MIR200C (microRNA 200c)

2014-07-01   Merve Mutlu , Özge Saatçi , Umar Raza , Erol Eyüpoglu , Emre Yurdusev , Özgür Sahin 




MicroRNAs (miRNAs) are 20-22 nucleotide long small non-coding RNAs and have a function of regulation of gene postranscriptionally via targeting mainly the 3UTRs of the genes. miR-200c is a member of miR-200 family with 4 other family members (miR-200a, miR-200b, miR-429 and miR-141) located in chromosome 12 (12q13.31) together with miR-141. miRNAs can be classified as oncomiRs and tumor suppressors according to their target gene and which tissue they are expressed. miR-200c has been shown to be a tumor suppressor in various cancer types. miR-200c has been initially shown to regulate epithelial-mesenchymal transition (EMT) by downregulating ZEB1\/2 and upregulating E-cadherin, known epithelial marker. Afterwards, it has been demonstrated that miR-200c also have other important functions in proliferation, cell cycle control, apoptosis, anoikis, invasion, and metastasis of cancer and also in other diseases. Furthermore, miR-200c is a well-established prognostic and diagnostic marker in different cancer types.


Atlas Image
A. Stem-loop structure of hsa-mir-200c (precursor miRNA). B. The miR-200 family members. The human miR-200 family is located in two fragile chromosomal regions on 1p36.33 (200b, 200a and 429) and 12p13.31 (200c and 141), respectively. It consists of two clusters based on seed sequence similarity: miR-200bc/429 (red) and 200a/141 (blue), distinguished by a single nucleotide change (U to C) (source: Uhlmann et al., 2010, Oncogene).


miR-200c belongs to the miR-200 family, which consists of 5 members with two different chromosomal locations: miR-200c and miR-141 are located on chromosome 12p13 and miR-200a, miR-200b and miR-429 are located on 1p36. This family is frequently downregulated upon the progression of tumors and maps to fragile chromosomal regions. Members of this family are important regulators of epithelial-to-mesenchymal transition (EMT) and metastasis.


miRNAs are generally transcribed by RNA polymerase II.

hsa-mir-200c (precursor miRNA)
Accession: MI0000650
Length: 68 bp

hsa-miR-200c* (-5p) (mature miRNA)
Accession: MIMAT0004657
Length: 23

hsa-miR-200c-3p (mature miRNA)
Accession: MIMAT0000617
Length: 23


No reported pseudogenes.



microRNAs are not translated into proteins.

Implicated in

Entity name
Cancer development
Atlas Image
miR-200c targets several genes regulating numerous processes involved in cancer development and progression.
Entity name
Bladder cancer
Loss of miR-200c expression was found to be associated with disease progression and poor outcome in 100 stage T1 bladder tumor patients (Wiklund et al., 2011a). Urinary miR-200 family levels are repressed in patients with bladder cancer (Wang et al., 2012).
Deep sequencing of nine bladder urothelial carcinomas (BUC) and matched normal urothelium revealed that the miR-200c/141 cluster is upregulated in bladder cancer (Han et al., 2011). Consistently, a study comparing miRNA expression patterns by microarray in 27 invasive and 30 superficial bladder tumors with 11 normal urothelia found that miR-200c was upregulated in bladder tumors compared to normal urothelium; however, expression of miR-200c was reduced in invasive compared to non-invasive tumors due to promoter hypermethylation (Wiklund et al., 2011a). Furthermore, microarray miRNA analysis of 43 primary tumors (10 colon, 10 bladder, 13 breast and 10 lung cancers) and matched lymph node metastases revealed that miR-200c and other miR-200 family members are downregulated in metastases compared to primary tumors (Baffa et al., 2009).
Mechanistically, miR-200c has been implicated in the regulation of epithelial-to-mesenchymal transition (EMT) in bladder cancer cells. A comparison of nine bladder cancer cell lines revealed a correlation between high expression of miR-200c (and fellow miR-200 family member miR-200b) and epithelial phenotype (Adam et al., 2009). The same study also reported that miR-200c expression reverses resistance to anti-EGFR therapy in bladder cancer cell lines through targeting ERRFI-1.
However, contradictory to these results, in another study, it was found that the levels of miR-200c was upregulated in infiltrating BUC patients as compared with non-infiltrating BUC patients (Xie et al., 2012). These results were supported in a recent study, which again demonstrated that the levels of miR-200c were significantly higher in infiltrating carcinoma than in high grade bladder tumors (Lee et al., 2014).
Entity name
Breast cancer
Diagnosis. Circulating tumor cell (CTC)-positive metastatic breast cancer patients had significantly higher levels of miR-200c than CTC-negative metastatic breast cancer patients and miR-200c along with some other miRNAs were suggested to be potential predictive markers for CTC status of metastatic breast cancer patients (Madhavan et al., 2012).
miR-200c was found to be downregulated in breast cancer patients that are irresponsive to neoadjuvant chemotherapy than patients who respond (Chen et al., 2013c).
A double-negative feedback loop between ZEB family transcription factors and the miR-200 family was shown to regulate EMT in different cell systems, including breast cancer cells (Burk et al., 2008). Moreover, expression of miR-200c was revealed to be activated by p53, resulting in induction of EMT in mammary epithelial cells upon loss of p53 (Chang et al., 2011). Loss of p53 was positively correlated with expression of ZEB1 and negatively correlated with expression of miR-200c and E-Cadherin in 106 breast tumor specimens.
miRNA microarray analysis of 43 primary tumors (10 colon, 10 bladder, 13 breast and 10 lung cancers) and matched lymph node metastases revealed that miR-200c and other miR-200 family members are downregulated in metastases compared to primary tumors (Baffa et al., 2009). Moreover, miR-200c and other miR-200 family members were shown to be underexpressed in the aggressive claudin-low subtype of breast cancer, which displays an EMT-like gene expression signature (Herschkowitz et al., 2011). In contrast, luminal breast cancers, which have a more epithelial-like phenotype and a better clinical prognosis, express high levels of miR-200c (Bockmeyer et al., 2011). Besides ZEB family, miR-200c can modify metastasis by targeting HMGB1, ZNF217 and a truncated form of VEGFR-1 (Chang et al., 2014a; Bai et al., 2014b; Mezquita et al., 2014). miR-200c was also found to be an inhibitor of tumor progression and therapy resistance by targeting KRAS and ZNF217 (Bai et al., 2014b; Kopp et al., 2014).
Re-expression of the miR-200 family in aggressive breast cancer cells was shown to inhibit experimental lung metastasis (Ahmad et al., 2011) and decreased expression of it is associated with lymph node metastases in triple negative breast cancer (Berber et al., 2014). In contrast, another study reported that miR-200c is upregulated in breast cancer patients with lymph node metastasis (Wang et al., 2013). It was also shown to promote colonization of breast cancer cells (Dykxhoorn et al., 2009). The level of miR-200c was also found to be high in patients with various cancers including breast cancer that develop poly-metastases and it was reasoned that miR-200c is aiding colonization in the late stages of metastasis by reverting EMT (Lussier et al., 2011). In in vitro assays, miR-200c suppresses migration and invasion of breast cancer cells through various mechanisms, including targeting of ZEB1/ZEB2, PLCG1, moesin and fibronectin (Korpal et al., 2008; Uhlmann et al., 2010; Howe et al., 2011; Gerhauser, 2013).
miR-200c also targets stem cell factors such as BMI1, and downregulation of miR-200c was shown to be characteristic of breast cancer stem cells (Shimono et al., 2009) and DNA methylation was found to be the cause of the repression in breast cancer stem cell like populations (Lim et al., 2013). A natural compound, resveratrol, is increasing the activity of Ago2 and as a result inhibiting breast cancer stem cell-like characteristics by increasing the activity of tumor suppressor miRNAs including miR-200c (Hagiwara et al., 2012).
Furthermore, miRNA microarray analysis revealed that miR-200c is downregulated in breast cancer cells with acquired resistance to cisplatin (Pogribny et al., 2010). It was also found to be downregulated in doxorubicin resistant MCF-7 and BT474 breast cancer cells (Chen et al., 2013c; Kopp et al., 2012). It was also associated with trastuzumab resistance, which was found to be reverse by upregulation of miR-200c through the blockage of TGF-B signaling (Bai et al., 2014b).
miR-200c is also associated with increase in radiosensitivity in breast cancer cells by inhibiting cell proliferation, and by increasing apoptosis and DNA double-strand breaks. TBK1 was found to be a direct target of miR-200c and its downregulation by miR-200c is partially responsible for increased apoptosis (Lin et al., 2013).
Entity name
CAFs and microenvironment
Eleven dysregulated miRNAs including miR-200c were identified in cancer-associated fibroblasts (CAFs) cultured from six resected breast tumor tissues that had not previously received radiotherapy or chemotherapy treatment. MiR-200c was found to be up-regulated in CAFs compared to normal fibroblasts (NFs) (Zhao et al., 2012). miR-200c targets Flt1/VEGFR1 gene which play an important role in enhancement of cell invasion in CAFs isolated from murine lung adenocarcinomas (Roybal et al., 2011).
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Colorectal cancer
Kaplan-Meier survival analysis of 24 colorectal cancer patients suggested that high expression of miR-200c was associated with decreased overall survival (Xi et al., 2006). miR-200c levels in plasma and serum can serve as a potential noninvasive biomarker for CRC prognosis/screening and predicting metastasis (Zhang et al., 2013; Toiyama et al., 2014). Fluoropyrimidines treated two separate groups of individuals showed high levels of miR-200c, along with other members of miR-200 family, and found associated with longer overall and disease-free survival (Diaz et al., 2014).
Analysis of miR-200c expression in 24 colorectal cancer (CRC) biopsies and matched normal samples by qRT-PCR revealed that miR-200c is overexpressed in CRC tumors compared to normal tissue (Xi et al., 2006). Furthermore, microarray miRNA analysis of 43 primary tumors (10 colon, 10 bladder, 13 breast and 10 lung cancers) and matched lymph node metastases revealed that miR-200c and other miR-200 family members are downregulated in metastases compared to primary tumors (Baffa et al., 2009). miR-200c was also among miRNAs found upregulated in CRC tissue as compared to normal colonic mucosa shown in a microarray analysis followed by RT-PCR (Tsunoda et al., 2011). K-Ras driven expression of miR-200c and other miRNAs in a 3D culture specific manner suggested a role for miR-200c in regulating colorectal tumor development in vivo (Tsunoda et al., 2011; Ota et al., 2012). In an independent study, miR-200c was found to be associated with the development of CRC (Chen et al., 2012). By directly tageting ZEB1, miR-200c inhibited metastasis in CRC cells SW480/620 (Chen et al., 2012). Epigenetically regulated low expression of miR-200c contributes to EMT and metastatic potential of CRC, and transfecting CRC cells lines with miR-200c lead to increased proliferation but reduced invasion and migration (Hur et al., 2013). miR-200c regulates Sox2 expression in a negative feedback loop in CRC and this regulation is associated with stemness, growth and metastatic potential of CRC (Lu et al., 2014). On the contrary, miR-200c has also been shown to work as oncogene in CRC where it takes part in inhibiting apoptosis and its silencing leads towards upregulation of Pten and p53 tumor suppressor genes (Chen et al., 2014b).
Entity name
Endometrial cancer
Endometrial carcinoma; endometrial carcinosarcoma.
miR-200c was shown to be a prognostic marker of overall survival. High levels of miR-200c were associated with lower chance of survival in patients with endometrioid endometrial cancer (Torres et al., 2013).
miRNA microarray analysis of four endometrial endometrioid carcinomas and four normal endometrial tissue samples showed that miR-200c and other miR-200 family members were overexpressed in cancerous compared to normal tissue (Lee et al., 2011). These results were supported by other studies which showed that miR-200c expression is significantly upregulated in endometrial tumors compared to normal tissues (Karaayvaz et al., 2012) as well as to complex atypical hyperplasia (CAH) and simple hyperplasia (SH) cases (Lee et al., 2012). Inhibition of miR-200c decreased the growth of endometrial carcinoma cells (Lee et al., 2011). It was shown that it inhibits the expression of BRD7, which was reported as a potential tumor suppressor gene that prevents B-catenin from entering into nuclues. Inhibition of BRD7 by miR-200c results in increased expression of B-catenin transcriptional target genes, cyclin D1 and c-myc (Park et al., 2012). Inhibition of miR-200c decreased the growth of endometrial carcinoma cells (Lee et al., 2011). In contrast, an analysis of miR-200c expression levels in five endometrial cancer and normal endometrial cell lines suggested that miR-200c is lower in cell lines derived from aggressive cancer compared to those derived from less aggressive cancer or normal endometrial epithelium (Cochrane et al., 2009). Restoration of miR-200c expression in aggressive endometrial cancer cells reduced their migration and invasion and increased their sensitivity to microtubule-targeting chemotherapeutic agents, at least in part through targeting TUBB3 (Cochrane et al., 2009; Cochrane et al., 2010; Howe et al., 2011). In a panel of 23 endometrial carcinosarcomas, which are composed of mixed populations of epithelial-like and mesenchymal-like cells, miR-200c and other miR-200 family members were found to be downregulated in the mesenchymal components of the tumors compared to the epithelial components (Castilla et al., 2011) and it was found to be methylated during EMT in both in vitro and in vivo models (Díaz-Martín et al., 2014). These results are consistent with the established role of the miR-200 family in suppression of epithelial- mesenchymal transition.
Entity name
Esophageal cancer
In a panel of 98 esophageal cancer patients treated with preoperative chemotherapy and surgery, expression of miR-200c was associated with shortened overall survival and poor response to chemotherapy, potentially through upregulation of the Akt signaling pathway (Hamano et al., 2011). In another study higher miR-200c expression in serum collected from 64 esophageal cancer patients who have received neoadjuvant chemotherapy has shown to be associated with poor response to chemotherapy and shortened progression free survival (Tanaka et al., 2013).
qRT-PCR analysis of miR-200 expression levels in 17 patients with Barretts esophagus and 20 patients with esophageal adenocarcinoma indicated that miR-200c is downregulated during cancer progression from normal epithelium through Barretts esophagus to esophageal adenocarcinoma (Smith et al., 2011). In contrast, another study on 98 esophageal cancer patients treated with preoperative chemotherapy and surgery found that miR-200c was expressed at higher levels in the tumor than in normal tissue (Hamano et al., 2011).
Entity name
Gastric cancer
Significantly higher expression level of miR-200c in blood has been observed in gastric cancer patients as compared to controls and also found as good predictor of overall and progression free survival in gastric cancer patients (Valladares-Ayerbes et al., 2012). miR-200c, mir-200b and miR-125 were found to be targeting most of the genes driving mesenchymal subtype of gastric cancer; a subtype which is associated with poor overall survival in gastric cancer. Functional analysis showed that miR-200b suppresses ZEB1, augments E-cadherin and inhibit cell migration and tumor growth in a mouse model (Song et al., 2014).
Three miRNAs from miR-200 family (miR-200a, -200b, -200c) found downregulated in gastric adenocarcinoma and miR-200a, when upregulated, suppressed EMT and tumor growth by modulating Wnt/β-catenin signaling pathway through targeting ZEB1 and ZEB2 (Cong et al., 2013). Co-delivering miR-200c with docetaxel by nanoparticles significantly enhanced cytotoxicity of docetaxel and suppressed tumor growth in vivo possibly by decreasing TUBB3 levels and by reversing EMT (Liu et al., 2013). miR-200b and miR-200c, when overexpressed in gastric cancer cells, reduced DNA methylation by targeting DNMT3A, DNMT3B and SP1, and also reduced tumor growth and migration capacity by re-expressing of p16, RASS1A1, and E-cadherin (Tang et al., 2013). Overexpressing miR-200c in gastric cancer tissues and cells (SGC7901 and SGC7901/DDP) led to enhancing cisplatin sensitivity in these cells possibly by targeting RhoE (Chang et al., 2014b). miR-141, another member of miR-200 family, also found suppressing proliferation, colony formation, migration and invasion capabilities of gastric cancer cells partially by targeting HDGF (Chen et al., 2014a). A study conducted on miRNA binding site SNPs located in the 3UTRs of genes involved in gastric cancer susceptibility revealed that ephrin-A1 (EFNA1) gene is significantly associated with risk of gastric cancer as miR-200c binding site SNP (rs12904 G>A) in the 3UTR of EFNA1 can significantly modulate EFNA1 expression (Li et al., 2014b).
Entity name
Germ cell tumors
Germinoma; yolk sac tumors.
Diagnosis. Microarray analysis of 25 germ cell tumors and subsequent validation by qRT-PCR in 10 independent samples identified miR-200c overexpression in yolk sac tumors compared to germinoma (Murray et al., 2010).
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Head and neck cancer
Squamous cell carcinoma; spindle cell carcinoma.
miR-200c was significantly downregulated in a panel of 30 spindle cell carcinomas (which display a mesenchymal-like phenotype) compared to normal mucosa as determined by qRT-PCR (Zidar et al., 2011). In contrast, expression levels of miR-200c in 30 squamous cell carcinomas were comparable to normal tissue. A xenotransplantation study has shown that miR-200c directly targets BMI1 and overexpression of miR-200c or BMI1 knockdown inhibited lung metastasis and prolonged the survival of mice suggesting therapeutic potential miR-200c in head and neck squamous cell carcinoma (Lo et al., 2011). HGF-driven downregulation of miR-200c leads to enhanced ZEB1/E-cadherin mediated epithelial to mesenchymal transition in head and neck squamous cell carcinoma (Susuki et al., 2011). miR-200c, along with other miRNAs, play important roles e.g., regulation of stemness and epithelial mesencymal transition in head and neck tumor cells (Tu et al., 2013). Targeting HPV 16 E6-p300 interaction with a CH1-domain inhibitor resulted in enhanced functional reactivation of p53 tumor suppressor as a result of upregulation of miR-200c and miR-34a expression levels (Xie et al., 2014). In head and neck squamous cell carcinoma, promoter hypermethylation of miR-200c targets (Zeb1/Zeb2) has been reported to somehow mask the effects associated with miR-200 family regulation of EMT and migration (Tamagawa et al., 2014).
Entity name
Huntington disease
A significant alteration of miR-200 family members, miR-200a, and miR-200c has been observed in the cerebral cortex and the striatum, at the early stage of disease progression in a mouse model of Huntingtons disease. Elevated levels of miR-200c results in downregulation of some target genes, which have been suggested to play important roles in synaptic function, axonal trafficking, neurotransmitter release, neurogenesis, and neuronal survival (Jin et al., 2012).
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It was found that TIMP2, FBLN5, and VEGFA as direct targets of miR-200c in leiomyomas and the expression of miR-200c was significantly lower in leiomymas compared to matched myometrium (Chuang et al., 2012).
Entity name
Liver cancer
Diagnosis. miR-200c has been suggested as a biomarker to distinguish hepatocellular carcinoma from liver metastases (Barshack et al., 2010).
miR-429, a member of miR-200 family, was shown to be a prognostic marker in a hepatocellular carcinoma (HCC) tissue microarray study as it was upregulated and shown to promote liver tumor initiating cell properties by targeting Rb binding protein 4 (Li et al., 2014a).
miRNA microarray analysis of 92 primary hepatocellular carcinomas and 9 HCC cell lines identified miR-200c as a microRNA that is upregulated by p53 (Kim et al., 2011). Increased expression of miR-200c results in downregulation of transcriptional repressors ZEB1 and ZEB2, suggesting a role for p53-mediated regulation of miR-200c in suppression of EMT. miR-200c was reported to be underexpressed in benign liver tumors compared to HCC (Ladeiro et al., 2008); miR-200c levels were determined by qRT-PCR in two sets of tumors (first set: 18 benign tumors, 28 hepatocellular carcinomas; second set: 12 benign tumors, 22 hepatocellular carcinomas). miR-200c, along with other miRNAs, was found to be downregulated in both HCC and intrahepatic cholangiocarcinoma (ICC) (Karakatsanis et al., 2013). Targeting liver cancer cells with miR-200b, member of miR-200 family, not alone but simultaneously with DNA methyl transferase inhibitor reduced the metastatic potential of these cells irrespective of E-cadherin levels (Ding et al., 2012). Transcriptome profiling of 23 ICC and combined HCC tumor specimens using microarrays have revealed miR-200c/EMT as common signaling pathway activated in ICC stem cells. Furthermore, NCAM1, known hepatic stem cell marker, was found to be a direct target of miR-200c (Oishi et al., 2012). While analyzing the expression of a member of miR-200 family, miR-429, in 138 pathology diagnosed HCC patients, this miRNA was found upregulated in tumor tissues and contributing to cell proliferation and inhibiting apoptosis (Huang et al., 2013). Simultaneous silencing of miR-141 and miR-200c has been reported to be responsible for developing HCC with bile duct tumor thrombosis by activation of ZEB-1 mediated EMT in a study conducted on patients having HCC with or without bile duct tumor thrombus (Yeh et al., 2014).
Entity name
Lung cancer
qRT-PCR analysis of miR-200c expression levels in 70 non-small cell lung cancer (NSCLC) patients revealed that high expression of miR-200c was associated with reduced overall survival (Liu et al., 2011). Another study investigated serum microRNAs as cancer biomarkers showed that miR200c is associated with NSCLC, suggesting a potential usage for diagnosis (Liu et al., 2012b). Re-expression of miR-200 family miRNAs has been found to target and downregulate the previously identified prognostic biomarkers in metastatic NSCLC suggesting the importance of these miRNAs in regulating metastatic potential of lung cancer (Pacurari et al., 2013).
Treatment of immortalized human bronchial epithelial cells with tobacco carcinogens was shown to induce an EMT-like phenotype and stem-cell like properties (Tellez et al., 2011). Quantification of miRNA levels by qRT-PCR in combination with bisulfite sequencing and chromatin immunoprecipitation revealed that these changes are accompanied by epigenetic silencing of miR-200c and other EMT-regulating microRNAs, suggesting that loss of miR-200c contributes to transformation of lung epithelial cells. In contrast, miRNA microarray analysis of six NSCLCs and matched adjacent normal tissue revealed that miR-200c is upregulated in NSCLC compared to healthy tissue (Liu et al., 2011). This finding was further validated in 70 lung carcinomas and matched normal tissue by qRT-PCR.
Several studies have reported that miR-200c can repress invasion and metastasis of lung cancer cells. Firstly, low expression of miR-200c and other miR-200 family members was associated with increased metastatic potential in a syngeneic mouse model of lung adenocarcinoma, and re-expression of miR-200 family members in these cell lines prevented EMT and metastasis (Gibbons et al., 2009). Secondly, miR-200c was shown to be downregulated by promoter hypermethylation in invasive NSCLC cell lines, and re-expression of miR-200c reduced the invasive potential of these cell lines (Ceppi et al., 2010). Furthermore, microarray miRNA analysis of 43 primary tumors (10 colon, 10 bladder, 13 breast and 10 lung cancers) and matched lymph node metastases revealed that miR-200c and other miR-200 family members are downregulated in metastases compared to primary tumors (Baffa et al., 2009). Finally, low expression of miR-200c in 69 primary lung tumors was correlated with lymph node metastases (Ceppi et al., 2010).
Mechanistically, the Notch ligand Jagged2 was shown to suppress expression of miR-200 family members, resulting in induction of EMT and increased metastatic potential (Yang et al., 2011). Moreover, miR-200c and fellow miR-200 family member miR-200b target VEGFR, which also contributes to invasion and metastasis (Roybal et al., 2011).
It was demonstrated that miR-200c which is normally downregulated in lung cancer tissue, is upregulated by transfection in H460 cells resulted in higher levels of apoptotic cells in comparison with untransfected ones (Bai et al., 2014a). In addition, miR-200c enhanced the antitumor effect of reservatol (RESV). Drug sensitivity can be restored in EMT driven erlotinib (EGFR inhibitor) resistant NSCLC by using a single agent, silibinin, which fully reverses the high miR-21/low miR-200c signature and represses mesenchymal markers SNAIL, ZEB and N-Cadherin (Cufí et al., 2013). Moreover, VEGF family is an important regulator of angiogenesis and VEGFR2 has been identified as direct target of miR-200c. Ectopic miR-200c expression radio-sensitized the A549 cells by VEGF-VEGFR2 pathway leading to inhibition of its downstream pro-survival signaling and angiogenesis (Shi et al., 2013). Finally, acquired resistance to EGFR inhibitors in lung cancer cells is found to be associated with EMT (characterized by downregulation of miR-200c) and/or stem like properties (increased ALDH1A1 levels, increase of side population and self renewal capability) (Shien et al., 2013).
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High expression levels of miR-200c was found to be associated with decreased overall survival and time from initial diagnosis to the first relapse in diffuse large B-cell lymphoma (DLBCL) (Berglund et al., 2013).
miR-200c was found directly targeting polycomb protein BMI1 In radiation induced thymic lymphoma (RITL) model of BALB/c mice and adenovirus mediated overexpression of miR-200c reduced tumorigenesis in vivo suggesting it as a novel therapeutic method to treat RITL (Cui et al., 2014). Genome-wide expression profiling of nine H. pylori-positive and nine H. pylori-negative gastric diffuse large B-cell lymphomas and further confirmation in 30 samples for each has revealed that miR-200c inhibits ZEB1 in H. pylori-positive gastric diffuse large B-cell lymphoma which, in turn, upregulates BCL6 and results in less aggressive behavior of H. pylori-positive gastric diffuse large B-cell lymphomas (Huang et al., 2014).
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Malignant pleural mesothelioma
Diagnosis. miR-200c has been proposed as a biomarker to distinguish malignant pleural mesothelioma from lung adenocarcinoma and lung metastases of other carcinomas. miRNA microarray expression profiling of 10 lung adenocarcinomas and 15 mesotheliomas revealed that miR-200c is reduced in mesothelioma (Gee et al., 2010). This result was further confirmed by qRT-PCR in a set of 100 mesotheliomas and 32 lung adenocarcinomas. Similarly, microRNA microarray analysis of 7 malignant pleural mesotheliomas and 97 carcinomas of various origins also identified miR-200c as underexpressed in mesotheliomas compared to the carcinoma samples, and differential expression levels of miR-200c and two other microRNAs could successfully be used to distinguish between malignant pleural mesothelioma and other types of cancer (Benjamin et al., 2010).
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Analysis of miR-200c expression levels in a panel of 10 melanoma cell lines by qRT-PCR showed that miR-200c is overexpressed in many of these cell lines compared to normal melanocytes (Elson-Schwab et al., 2010). On the contrary, overexpression of miR-200c in melanoma cells significantly decreased proliferation, migratory capacity and drug resistance by targeting BMI-1, ABCG2, ABCG5, and MDR1 and enhancing E-cadherin levels. Overexpression of miR-200c also inhibited melanoma xenograft growth and metastasis in vivo (Liu et al., 2012a). Decreased levels of miR-200a, miR-200c, and miR-203 correlated with increasing tumor thickness in a series of 23 frozen primary melanomas. A functional validation study using an anti-miR200 strategy demonstrated that loss of miR-200 expression in melanoma cell lines reduced E-cadherin expression (van Kempen et al., 2012). Overexpressing miR-200c in mouse melanoma B16F10 CD44+CD133+ CSCs led to the reduced cell proliferation, colony formation, cell migration and invasion potential in vitro as well as tumorigenicity in vivo but not in B16F10 cells and B16F10 non-CD44+ CD133+ CSCs (Dou et al., 2013).
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Oral squamous carcinoma
Significant expression alteration of miR-200 family including miR-200c was shown in oral squamous carcinoma patients compared to healthy controls tested from saliva. This demonstrates a potential biomarker property of miR-200c that can be used in clinical application with oral rinse (Wiklund et al., 2011b).
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Ovarian cancer
High expression of miR-200c was found correlated with decreased progression-free and overall survival in a panel of 20 serous ovarian cancer patients (Nam et al., 2008). In contrast, a study investigating microRNA expression profiles in a total of 144 patients with epithelial ovarian cancer found that low expression of miR-200c was associated with increased progression-free and overall survival (Marchini et al., 2011). Similarly, high expression of miR-200c was correlated with response to chemotherapy and decreased risk of disease recurrence in a panel of 57 patients with serous ovarian carcinoma (Leskela et al., 2010). In a study for identification of differentially expressed miRNAs in high-grade serous ovarian carcinoma (HGSC), clear cell ovarian carcinoma (CCC) and ovarian surface epithelium (OSE), high miR-200c-3p expression has been associated with poor progression-free (p = 0.031) and overall (p = 0.026) survival in HGSC patients (Kim et al., 2014).
Diagnosis. MiR-200c along with other miR-200 family miRNAs (miR-141, miR-200a, miR-200b) has been found preferentially upregulated in epithelial ovarian cancer suggesting its role as a potential biomarker for this cancer type (Chen et al., 2013d).
miR-200c was found to be overexpressed in a panel of 20 serous ovarian carcinomas compared to 8 normal ovarian tissues by miRNA microarray analysis (Nam et al., 2008). Similarly, increased expression of miR-200c compared to normal ovary (n=15) was reported for serous, endometrioid and clear cell ovarian carcinoma in a series of 69 cancer specimens.
Expression of miR-200c was correlated with E-Cadherin levels in 36 primary ovarian carcinomas (Park et al., 2008). The regulatory effect of miR-200c on EMT has been shown to be mediated through targeting of ZEB1 and ZEB2, which transcriptionally repress E-Cadherin (Gregory et al., 2008; Korpal et al., 2008; Park et al., 2008). In this same line of comparative study, miRNA microarray and qPCR analysis, it has been shown elevated expression level of miR-200c on ovarian carcinoma effusions (Vaksman et al., 2011).
Re-expression of miR-200c in aggressive ovarian cancer cell lines was shown to reduce their migratory capacity; however, this effect appears to be independent of E-Cadherin expression (Cochrane et al., 2010). Furthermore, forced expression of miR-200c has been reported to sensitize ovarian cancer cells to paclitaxel treatment due to downregulation of miR-200c target gene TUBB3 (Cochrane et al., 2009; Cochrane et al., 2010). Reduction in endogenous PTEN levels and upregulation of phopho-Akt levels were reported in miR-200c transfected ovarian cancer stem cells (OCSCs) (Luo et al., 2013). miR-200c was also shown to be downregulated in a subpopulation of the ovarian cancer cell line OVCAR3 expressing the cancer stem cell marker CD133 (Guo et al., 2011). In CD117+ CD44+ OCSCs, miR-200c expression has been reduced. Overexpression of miR-200c in these OCSCs upregulated E-cadherin expression, downregulated ZEB-1 and Vimentin expression in vitro. Also miR-200c upregulation showed inhibitory effect in CD117+ CD44+ OCSCs in xenograft growth and lung metastasis in nude mice (Chen et al., 2013b).
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Pancreatic cancer
In a panel of 99 pancreatic cancer patients, high expression of miR-200c was associated with increased overall survival (Yu et al., 2010).
Downregulation of miR-200c and other miR-200 family members has been observed in gemcitabine-resistant pancreatic cancer cell lines (Li et al., 2009; Ali et al., 2010). miR-200c has also been suggested to have a stemness-inhibiting function in pancreatic cancer cells through targeting of stem cell factors such as Bmi1 (Wellner et al., 2009).
A double-negative feedback loop between ZEB family transcription factors and the miR-200 family was shown to regulate EMT in different cell systems, including pancreatic cancer cells (Burk et al., 2008). Consistently, high expression of miR-200c was shown to be associated with decreased invasive behavior in a panel of six pancreatic cancer cell lines, and miR-200c expression was correlated with E-Cadherin levels in pancreatic cancer specimens and cell lines (Yu et al., 2010). Overexpression of miR-200c in pancreatic cancer cell lines resulted in upregulation of E-Cadherin expression and reduced invasion but stimulated proliferation.
miRNA expression profiling of various stages in a mouse model of multistep tumorigenesis of the pancreas revealed that miR-200c is downregulated in metastases and metastasis-like tumors (Olson et al., 2009). Moreover, miR-200c also targets components of the Notch pathway, which is aberrantly activated in pancreatic cancer (Brabletz et al., 2011). Undifferentiated, aggressive pancreatic adenocarcinomas were shown to have higher expression of ZEB1 and Notch pathway components and lower expression of miR-200c compared to differentiated tumors.
In contrast to the studies described above, which suggest a metastasis-suppressing function for miR-200c in pancreatic cancer, a comparison of 16 pancreatic ductal adenocarcinoma cell lines found that miR-200c expression was upregulated in the highly metastatic cell lines (Mees et al., 2010). Interaction of MUC1 and ZEB1 at the promoter of miR-200c/141, results in transcriptional repression of these miRNAs leading to enhanced progression of pancreatic cancer (Mohr et al., 2013). In addition to regulation of proteins that modulate EMT in pancreatic adenocarcinoma, miR-200c has also been found to target cell surface mucins (MUC4 and MUC16), which play essential role in progression and metastasis in pancreatic adenocarcinoma (Radhakrishnan et al., 2013). In another study it was shown how metformin provokes the death of cancer stem cells in human pancreatic cancer cells (Bao et al., 2012). It was further demonstrated that metformin depleted a set of expression of cancer stem cell markers together with repression of miRNAS including miR-200c.
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Prolactinoma cancer
miR-200c was shown to be upregulated in a rat prolactinoma cell line, MMQ. A marine drug SZ-685C induces apoptosis of these cells via downregulation of miR-200c. Moreover, overexpression of miR-200c was found to be attenuating the apoptotic effect of SZ-685C (Chen et al., 2013a).
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Prostate cancer
Plasma levels of miR-200c has been identified as a potential biomarker to differentiate localized prostate cancer from metastatic castration resistant prostate cancer (Watahiki et al., 2013).
miRNA sequencing demostrated that miR-200c was upregulated in primary prostate carcinoma tissue (Szczyrba et al., 2011). In contrast, prostate cancer cells with EMT phenotype were found to have stem-cell like properties and express low levels of miR-200 family members (Kong et al., 2010). In approximately 50% of prostate cancer patients, chromosomal translocations that juxtapose the androgen-sensitive transmembrane protease, serine 2 (TMPRSS2) gene promoter to the oncogenic ETS-family transcription factor ERG result in excessive ERG overexpression which in turn directly represses miR-200c and promotes EMT by upregulating ZEB1 (Kim et al., 2013). Overexpression of miR-200c reversed EMT and stem-cell like properties, in part due to targeting of Notch-1. miR-200c was also shown to target the Notch ligand Jagged1, resulting in decreased proliferation of metastatic prostate cancer cells (Vallejo et al., 2011).
Entity name
Renal cancer
Clear cell carcinoma (CCC); chromophobe renal cell carcinoma (ChCC).
Diagnosis. miR-200c has been found to be specifically expressed in ChCC and has been suggested as one of the microRNAs that can be used to distinguish between RCC subtypes (Fridman et al., 2010). In addition, miR-200c is one of the five miRNAs used as a biomarker subset allowing to characterize clear-cell renal cell carcinoma (ccRCC), papillary RCC (pRCC) types 1 and 2 and normal tissue with high accuracy (Wach et al., 2013).
miR-200c was found to be significantly downregulated in CCC compared to normal kidney in a panel of 16 CCCs, 4 ChCCs and 6 normal kidneys both by microarray analysis and by qRT-PCR (Nakada et al., 2008). Furthermore, miR-200c expression was inversely correlated with expression of its target gene ZEB1 in these specimens. The downregulation of miR-200c in CCC was also confirmed by a second study comparing a total of 25 CCC and matched adjacent normal tissue (Liu et al., 2010). miR-200c has also been shown to be one of the most downregulated miRNAs in a comparative study with 70 matched pairs of clear cell renal cell carcinoma and normal kidney tissues (White et al., 2011).
miR-200c negatively affects metastasis of RCC cells by upregulating E-cadherin upon ZEB1 in addition to its effective role on AKT protein. Hence, AKT-miR-200c-E-cadherin pathway may have importance in EMT within RCC. In a series of functional studies of mir-200c, it has been shown that induction of miR-200c expression by Ochratoxin A (OTA) in porcine renal proximal tubular cells attenuates Nrf2 and HO-1 expression and elevates ROS and profibrotic TGF-β expression (Stachurska et al., 2013). Furthermore, it has been demonstrated that the renal cortical content of miR-200c was increased with aging. Increased miR-200c contents were associated with reduced expression of its target, ZEB2 (Sataranatarajan et al., 2012). Finally, multidrug resistance linked proteins appears to be prominently influenced by a set of five miRNAs including mir-200c used to discriminate renal tumor from normal tissue (Wach et al., 2013).
Entity name
Thyroid carcinoma
Diagnosis. Deregulated miR-200c, along with other miRNAs, has been reported as a marker for metastatic medullary thyroid carcinoma (Santarpia et al., 2013).
The expression of miR-200 family members, including miR-200c, was found to be downregulated in undifferentiated, aggressive anaplastic thyroid carcinoma compared to both normal tissue and well-differentiated papillary and follicular thyroid carcinomas (Braun et al., 2010). Overexpression of the miR-200 family induced mesenchymal-to-epithelial transition and reduced invasion of ATC cells. Overexpression of mir-200c in metastatic medullary thyroid carcinoma improves E-cadherin levels by directly targeting ZEB1 and ZEB2 or by enhanced expression of TGF-β (Santarpia et al., 2013).
Entity name
Wilms tumor
miRNA expression was analyzed in tissue samples including alveolar rhabdomyosarcoma (RMA) and malignant rhabdoid tumor (MRT) as well as in the rhabdomyosarcoma (RMS) cell lines (Rh30 and RD). It has been shown that miR-200c expression inhibits migration, and miR-200c was shown be expressed at a lower level in RMA than in MRT (Armeanu-Ebinger et al., 2012).
Entity name
The intestinal levels of miR-200c, together with 5 other miRNAs, varied upon Listeria infection and for 5 of these miRNAs including miR-200c, this alteration was found to be dependent on the presence of intestinal microbiota of mice (Archambaud et al., 2013).
Entity name
microRNA expression analysis showed mouse miR-200c (mmu-miR-200c) downregulation in the presence of high fat diet in C57BLJ6 mice (Chartoumpekis et al., 2012). Leptin deficient ob/ob mice manifest up-regulated miR-200a, miR-200b and miR-429 levels and leptin treatment decreases the amount of these miRNAs. Besides, through overexpression and downregulation studies it was shown that miR-200a might be a target for obesity since its inverse expression relationship with leptin and insulin signaling (Crépin et al., 2014).
Entity name
Stem cells, differentiation and reprogramming
Direct transfection of three mature miRNAs (mir-200c, -302s and -369s) with increased expression levels in embryonic stem cells and induced pluripotent stem cells can reprogram mouse and human cells to pluripotency. Transfection of miRNAs reduced the risk of mutations and tumorigenesis compared to induced pluripotent stem cells (IPSCs) by introduction of four transcription factors Oct3/4, Sox2, c-Myc and Klf4 (Miyoshi et al., 2011; Miyazaki et al., 2012). miR-200 family also regulates two of the Yamanaka factors Oct4/Sox2 in a specific manner and induces somatic cell reprogramming with the involvement of the miR-200/ZEB2 pathway (Wang et al., 2013). miR-200c, along with miR-150, has been reported to play an important role in human embryonic stem cell differentiation towards endothelial lineage and chick embryonic blood vessel formation by targeting ZEB1 (Luo et al., 2013).


Pubmed IDLast YearTitleAuthors
196718452009miR-200 expression regulates epithelial-to-mesenchymal transition in bladder cancer cells and reverses resistance to epidermal growth factor receptor therapy.Adam L et al
213890932011Phosphoglucose isomerase/autocrine motility factor mediates epithelial-mesenchymal transition regulated by miR-200 in breast cancer cells.Ahmad A et al
203887822010Gemcitabine sensitivity can be induced in pancreatic cancer cells through modulation of miR-200 and miR-21 expression by curcumin or its analogue CDF.Ali S et al
243273392013The intestinal microbiota interferes with the microRNA response upon oral Listeria infection.Archambaud C et al
230004532012Differential expression of miRNAs in rhabdomyosarcoma and malignant rhabdoid tumor.Armeanu-Ebinger S et al
195937772009MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets.Baffa R et al
246479182014Synergistic antitumor activity of resveratrol and miR-200c in human lung cancer.Bai T et al
246155442014MiR-200c suppresses TGF-β signaling and counteracts trastuzumab resistance and metastasis by targeting ZNF217 and ZEB1 in breast cancer.Bai WD et al
220866812012Metformin inhibits cell proliferation, migration and invasion by attenuating CSC function mediated by deregulating miRNAs in pancreatic cancer cells.Bao B et al
206192232010Differential diagnosis of hepatocellular carcinoma from metastatic tumors in the liver using microRNA expression.Barshack I et al
208646372010A diagnostic assay based on microRNA expression accurately identifies malignant pleural mesothelioma.Benjamin H et al
250134352014miR-205 and miR-200c: Predictive Micro RNAs for Lymph Node Metastasis in Triple Negative Breast Cancer.Berber U et al
232325982013High expression of microRNA-200c predicts poor clinical outcome in diffuse large B-cell lymphoma.Berglund M et al
214093952011MicroRNA profiles of healthy basal and luminal mammary epithelial cells are distinct and reflected in different breast cancer subtypes.Bockmeyer CL et al
212248482011The ZEB1/miR-200 feedback loop controls Notch signalling in cancer cells.Brabletz S et al
204986322010Downregulation of microRNAs directs the EMT and invasive potential of anaplastic thyroid carcinomas.Braun J et al
184834862008A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells.Burk U et al
211256662011Micro-RNA signature of the epithelial-mesenchymal transition in endometrial carcinosarcoma.Castilla MÁ et al
206967522010Loss of miR-200c expression induces an aggressive, invasive, and chemoresistant phenotype in non-small cell lung cancer.Ceppi P et al
247109332014miR-200c inhibits metastasis of breast cancer cells by targeting HMGB1.Chang BP et al
213363072011p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs.Chang CJ et al
238214572014MicroRNA-200c regulates the sensitivity of chemotherapy of gastric cancer SGC7901/DDP cells by directly targeting RhoE.Chang L et al
224968732012Differential expression of microRNAs in adipose tissue after long-term high-fat diet-induced obesity in mice.Chartoumpekis DV et al
242767552014miR-141 suppresses proliferation and motility of gastric cancer cells by targeting HDGF.Chen B et al
233171002013A novel marine drug, SZ-685C, induces apoptosis of MMQ pituitary tumor cells by downregulating miR-200c.Chen CH et al
238421082013MicroRNA-200c overexpression inhibits tumorigenicity and metastasis of CD117+CD44+ ovarian cancer stem cells by regulating epithelial-mesenchymal transition.Chen D et al
246829332014The roles of miR-200c in colon cancer and associated molecular mechanisms.Chen J et al
224073102012miR-200c inhibits invasion and migration in human colon cancer cells SW480/620 by targeting ZEB1.Chen ML et al
235464502013miRNA-200c increases the sensitivity of breast cancer cells to doxorubicin through the suppression of E-cadherin-mediated PTEN/Akt signaling.Chen Y et al
239783032013Candidate microRNA biomarkers in human epithelial ovarian cancer: systematic review profiling studies and experimental validation.Chen Y et al
226852662012miR-200c is aberrantly expressed in leiomyomas in an ethnic-dependent manner and targets ZEBs, VEGFA, TIMP2, and FBLN5.Chuang TD et al
200491722010Loss of miR-200c: A Marker of Aggressiveness and Chemoresistance in Female Reproductive Cancers.Cochrane DR et al
233813892013Downregulated microRNA-200a promotes EMT and tumor growth through the wnt/β-catenin pathway by targeting the E-cadherin repressors ZEB1/ZEB2 in gastric adenocarcinoma.Cong N et al
243947572014The over-expression of miR-200a in the hypothalamus of ob/ob mice is linked to leptin and insulin signaling impairment.Crépin D et al
239632832013Silibinin suppresses EMT-driven erlotinib resistance by reversing the high miR-21/low miR-200c signature in vivo.Cufí S et al
243756602014Down regulation of miR200c promotes radiation-induced thymic lymphoma by targeting BMI1.Cui J et al
245105882014Role of miR-200 family members in survival of colorectal cancer patients treated with fluoropyrimidines.Diaz T et al
241222922014A core microRNA signature associated with inducers of the epithelial-to-mesenchymal transition.Díaz-Martín J et al
235526992012miR-200b restoration and DNA methyltransferase inhibitor block lung metastasis of mesenchymal-phenotype hepatocellular carcinoma.Ding W et al
241201132013Overexpression of microRna-200c in CD44+CD133+ CSCS inhibits the cellular migratory and invasion as well as tumorigenicity in mice.Dou J et al
197870692009miR-200 enhances mouse breast cancer cell colonization to form distant metastases.Dykxhoorn DM et al
209571762010MicroRNA-200 family members differentially regulate morphological plasticity and mode of melanoma cell invasion.Elson-Schwab I et al
205956292010Accurate molecular classification of renal tumors using microRNA expression.Fridman E et al
213512652010Downregulated microRNAs in the differential diagnosis of malignant pleural mesothelioma.Gee GV et al
236571532013Epigenetic impact of dietary isothiocyanates in cancer chemoprevention.Gerhauser C et al
197592622009Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression.Gibbons DL et al
183763962008The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1.Gregory PA et al
211099692011Description of the CD133+ subpopulation of the human ovarian cancer cell line OVCAR3.Guo R et al
224233222012Stilbene derivatives promote Ago2-dependent tumour-suppressive microRNA activity.Hagiwara K et al
212482972011Overexpression of miR-200c induces chemoresistance in esophageal cancers mediated through activation of the Akt signaling pathway.Hamano R et al
214649412011MicroRNA expression signatures of bladder cancer revealed by deep sequencing.Han Y et al
216330102012Comparative oncogenomics identifies breast tumors enriched in functional tumor-initiating cells.Herschkowitz JI et al
215015182011Targets of miR-200c mediate suppression of cell motility and anoikis resistance.Howe EN et al
243902222014Inhibition of ZEB1 by miR-200 characterizes Helicobacter pylori-positive gastric diffuse large B-cell lymphoma with a less aggressive behavior.Huang WT et al
242043822013MicroRNA-429 Modulates Hepatocellular Carcinoma Prognosis and Tumorigenesis.Huang XY et al
227355712013MicroRNA-200c modulates epithelial-to-mesenchymal transition (EMT) in human colorectal cancer metastasis.Hur K et al
229061252012Interrogation of brain miRNA and mRNA expression profiles reveals a molecular regulatory network that is perturbed by mutant huntingtin.Jin J et al
225147172012Prognostic significance of miR-205 in endometrial cancer.Karaayvaz M et al
222132362013Expression of microRNAs, miR-21, miR-31, miR-122, miR-145, miR-146a, miR-200c, miR-221, miR-222, and miR-223 in patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma and its prognostic significance.Karakatsanis A et al
241862052014TMPRSS2-ERG gene fusions induce prostate tumorigenesis by modulating microRNA miR-200c.Kim J et al
215187992011p53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB2.Kim T et al
245918192014Differential microRNA expression signatures and cell type-specific association with Taxol resistance in ovarian cancer cells.Kim YW et al
208059982010Epithelial to mesenchymal transition is mechanistically linked with stem cell signatures in prostate cancer cells.Kong D et al
232097482012miR-200c sensitizes breast cancer cells to doxorubicin treatment by decreasing TrkB and Bmi1 expression.Kopp F et al
243683372014The proto-oncogene KRAS is targeted by miR-200c.Kopp F et al
184112772008The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2.Korpal M et al
184330212008MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations.Ladeiro Y et al
227667952012Expression of miRNAs and PTEN in endometrial specimens ranging from histologically normal to hyperplasia and endometrial adenocarcinoma.Lee H et al
243069572014Expression of miRNAs and ZEB1 and ZEB2 correlates with histopathological grade in papillary urothelial tumors of the urinary bladder.Lee H et al
210351722011The expression of the miRNA-200 family in endometrial endometrioid carcinoma.Lee JW et al
210515602011The miR-200 family controls beta-tubulin III expression and is associated with paclitaxel-based treatment response and progression-free survival in ovarian cancer patients.Leskelä S et al
245721412015Epigenetic modification of MiR-429 promotes liver tumour-initiating cell properties by targeting Rb binding protein 4.Li L et al
230658162014G-A variant in miR-200c binding site of EFNA1 alters susceptibility to gastric cancer.Li Y et al
196542912009Up-regulation of miR-200 and let-7 by natural agents leads to the reversal of epithelial-to-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells.Li Y et al
235250112013Epigenetic modulation of the miR-200 family is associated with transition to a breast cancer stem-cell-like state.Lim YY et al
229911892013miR-200c enhances radiosensitivity of human breast cancer cells.Lin J et al
204207132010Identifying mRNA targets of microRNA dysregulated in cancer: with application to clear cell Renal Cell Carcinoma.Liu H et al
238069722013Targeted delivery of miR-200c/DOC to inhibit cancer stem cells and cancer cells by the gelatinases-stimuli nanoparticles.Liu Q et al
229824432012miR-200c inhibits melanoma progression and drug resistance through down-regulation of BMI-1.Liu S et al
215164862012High expression of serum miR-21 and tumor miR-200c associated with poor prognosis in patients with lung cancer.Liu XG et al
212941222011MicroRNA-200c attenuates tumour growth and metastasis of presumptive head and neck squamous cell carcinoma stem cells.Lo WL et al
246581572014Regulation of colorectal carcinoma stemness, growth, and metastasis by an miR-200c-Sox2-negative feedback loop mechanism.Lu YX et al
238697652013Enrichment of ovarian cancer stem-like cells is associated with epithelial to mesenchymal transition through an miRNA-activated AKT pathway.Luo X et al
221748562011MicroRNA expression characterizes oligometastasis(es).Lussier YA et al
218269962011[Differential expression of colon cancer microRNA in microarry study].Ma Q et al
229523442012Circulating miRNAs as surrogate markers for circulating tumor cells and prognostic markers in metastatic breast cancer.Madhavan D et al
213457252011Association between miR-200c and the survival of patients with stage I epithelial ovarian cancer: a retrospective study of two independent tumour tissue collections.Marchini S et al
195690502010EP300--a miRNA-regulated metastasis suppressor gene in ductal adenocarcinomas of the pancreas.Mees ST et al
247099042014Unlocking Doors without Keys: Activation of Src by Truncated C-terminal Intracellular Receptor Tyrosine Kinases Lacking Tyrosine Kinase Activity.Mezquita B et al
228263522012Emerging methods for preparing iPS cells.Miyazaki S et al
216207892011Reprogramming of mouse and human cells to pluripotency using mature microRNAs.Miyoshi N et al
241431672013MUC1 regulates expression of multiple microRNAs involved in pancreatic tumor progression, including the miR-200c/141 cluster.Mohr AM et al
210592072010The two most common histological subtypes of malignant germ cell tumour are distinguished by global microRNA profiles, associated with differential transcription factor expression.Murray MJ et al
189256462008Genome-wide microRNA expression profiling in renal cell carcinoma: significant down-regulation of miR-141 and miR-200c.Nakada C et al
184512332008MicroRNA expression profiles in serous ovarian carcinoma.Nam EJ et al
227074082012Transcriptomic profiling reveals hepatic stem-like gene signatures and interplay of miR-200c and epithelial-mesenchymal transition in intrahepatic cholangiocarcinoma.Oishi N et al
197592632009MicroRNA dynamics in the stages of tumorigenesis correlate with hallmark capabilities of cancer.Olson P et al
226416622012KRAS up-regulates the expression of miR-181a, miR-200c and miR-210 in a three-dimensional-specific manner in DLD-1 colorectal cancer cells.Ota T et al
237080872013The microRNA-200 family targets multiple non-small cell lung cancer prognostic markers in H1299 cells and BEAS-2B cells.Pacurari M et al
183818932008The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2.Park SM et al
220150432012The interactions between MicroRNA-200c and BRD7 in endometrial carcinoma.Park YA et al
200992762010Alterations of microRNAs and their targets are associated with acquired resistance of MCF-7 breast cancer cells to cisplatin.Pogribny IP et al
242045602013MicroRNA-200c modulates the expression of MUC4 and MUC16 by directly targeting their coding sequences in human pancreatic cancer.Radhakrishnan P et al
211157422011miR-200 Inhibits lung adenocarcinoma cell invasion and metastasis by targeting Flt1/VEGFR1.Roybal JD et al
241273322013A miRNA signature associated with human metastatic medullary thyroid carcinoma.Santarpia L et al
230201452012Molecular events in matrix protein metabolism in the aging kidney.Sataranatarajan K et al
242052062013MiR-200c increases the radiosensitivity of non-small-cell lung cancer cell line A549 by targeting VEGF-VEGFR2 pathway.Shi L et al
235423562013Acquired resistance to EGFR inhibitors is associated with a manifestation of stem cell-like properties in cancer cells.Shien K et al
196659782009Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells.Shimono Y et al
214483562011miR-200 family expression is downregulated upon neoplastic progression of Barrett's esophagus.Smith CM et al
243526452014Integrated microRNA network analyses identify a poor-prognosis subtype of gastric cancer characterized by the miR-200 family.Song F et al
232810302013Cross-talk between microRNAs, nuclear factor E2-related factor 2, and heme oxygenase-1 in ochratoxin A-induced toxic effects in renal proximal tubular epithelial cells.Stachurska A et al
218996612011Regulation of microRNA expression by hepatocyte growth factor in human head and neck squamous cell carcinoma.Susuki D et al
215931392011Downregulation of Sec23A protein by miRNA-375 in prostate carcinoma.Szczyrba J et al
244245722014Role of miR-200c/miR-141 in the regulation of epithelial-mesenchymal transition and migration in head and neck squamous cell carcinoma.Tamagawa S et al
238389162013Circulating miR-200c levels significantly predict response to chemotherapy and prognosis of patients undergoing neoadjuvant chemotherapy for esophageal cancer.Tanaka K et al
239958572013miR-200b and miR-200c as prognostic factors and mediators of gastric cancer cell progression.Tang H et al
213639152011EMT and stem cell-like properties associated with miR-205 and miR-200 epigenetic silencing are early manifestations during carcinogen-induced transformation of human lung epithelial cells.Tellez CS et al
239827502014Serum miR-200c is a novel prognostic and metastasis-predictive biomarker in patients with colorectal cancer.Toiyama Y et al
229872752013Diagnostic and prognostic significance of miRNA signatures in tissues and plasma of endometrioid endometrial carcinoma patients.Torres A et al
218731592011Oncogenic KRAS regulates miR-200c and miR-221/222 in a 3D-specific manner in colorectal cancer cells.Tsunoda T et al
233403062013MicroRNA aberrances in head and neck cancer: pathogenetic and clinical significance.Tu HF et al
205140232010miR-200bc/429 cluster targets PLCgamma1 and differentially regulates proliferation and EGF-driven invasion than miR-200a/141 in breast cancer.Uhlmann S et al
207161152011miRNA profiling along tumour progression in ovarian carcinoma.Vaksman O et al
229544172012Circulating miR-200c as a diagnostic and prognostic biomarker for gastric cancer.Valladares-Ayerbes M et al
212248472011Targeting Notch signalling by the conserved miR-8/200 microRNA family in development and cancer cells.Vallejo DM et al
237998492013MicroRNA profiles classify papillary renal cell carcinoma subtypes.Wach S et al
223862402012Expression of microRNAs in the urine of patients with bladder cancer.Wang G et al
236177472013Overexpressions of microRNA-9 and microRNA-200c in human breast cancers are associated with lymph node metastasis.Wang J et al
235749372013Plasma miRNAs as biomarkers to identify patients with castration-resistant metastatic prostate cancer.Watahiki A et al
199356492009The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs.Wellner U et al
217844682011miRNA profiling for clear cell renal cell carcinoma: biomarker discovery and identification of potential controls and consequences of miRNA dysregulation.White NM et al
221321512011MicroRNA alterations and associated aberrant DNA methylation patterns across multiple sample types in oral squamous cell carcinoma.Wiklund ED et al
221949842011A miR-200b/200c/429-binding site polymorphism in the 3' untranslated region of the AP-2α gene is associated with cisplatin resistance.Wu Y et al
180799882006Prognostic Values of microRNAs in Colorectal Cancer.Xi Y et al
228869732012Infiltration related miRNAs in bladder urothelial carcinoma.Xie P et al
234747632014Targeting HPV16 E6-p300 interaction reactivates p53 and inhibits the tumorigenicity of HPV-positive head and neck squamous cell carcinoma.Xie X et al
214034002011The Notch ligand Jagged2 promotes lung adenocarcinoma metastasis through a miR-200-dependent pathway in mice.Yang Y et al
241357222014Expression profile of microRNA-200 family in hepatocellular carcinoma with bile duct tumor thrombus.Yeh TS et al
205793952010MicroRNA, hsa-miR-200c, is an independent prognostic factor in pancreatic cancer and its upregulation inhibits pancreatic cancer invasion but increases cell proliferation.Yu J et al
246491792013Plasma miR-200c and miR-18a as potential biomarkers for the detection of colorectal carcinoma.Zhang GJ et al
229640232012MiRNA expression analysis of cancer-associated fibroblasts and normal fibroblasts in breast cancer.Zhao L et al
212374872011Down-regulation of microRNAs of the miR-200 family and miR-205, and an altered expression of classic and desmosomal cadherins in spindle cell carcinoma of the head and neck--hallmark of epithelial-mesenchymal transition.Zidar N et al
229563682012Loss of microRNA-200a and c, and microRNA-203 expression at the invasive front of primary cutaneous melanoma is associated with increased thickness and disease progression.van Kempen LC et al

Other Information

Locus ID:

NCBI: 406985
MIM: 612092
HGNC: 31580
Ensembl: ENSG00000207713


dbSNP: 406985
ClinVar: 406985
TCGA: ENSG00000207713



PathwaySourceExternal ID
MicroRNAs in cancerKEGGhsa05206
MicroRNAs in cancerKEGGko05206


Pubmed IDYearTitleCitations
215279372011miR-200c is upregulated by oxidative stress and induces endothelial cell apoptosis and senescence via ZEB1 inhibition.151
212248482011The ZEB1/miR-200 feedback loop controls Notch signalling in cancer cells.149
221445832012MicroRNA-200c represses migration and invasion of breast cancer cells by targeting actin-regulatory proteins FHOD1 and PPM1F.91
205140232010miR-200bc/429 cluster targets PLCgamma1 and differentially regulates proliferation and EGF-driven invasion than miR-200a/141 in breast cancer.77
206209602010miR-200c regulates induction of apoptosis through CD95 by targeting FAP-1.67
223647422012IL6-mediated suppression of miR-200c directs constitutive activation of inflammatory signaling circuit driving transformation and tumorigenesis.60
198016812009The miR200 family of microRNAs regulates WAVE3-dependent cancer cell invasion.56
229824432012miR-200c inhibits melanoma progression and drug resistance through down-regulation of BMI-1.55
257988332016The miR-200 family and the miR-183~96~182 cluster target Foxf2 to inhibit invasion and metastasis in lung cancers.54
235844752014MUC1-C oncoprotein activates the ZEB1/miR-200c regulatory loop and epithelial-mesenchymal transition.49


Merve Mutlu ; Özge Saatçi ; Umar Raza ; Erol Eyüpoglu ; Emre Yurdusev ; Özgür Sahin

MIR200C (microRNA 200c)

Atlas Genet Cytogenet Oncol Haematol. 2014-07-01

Online version: http://atlasgeneticsoncology.org/gene/51054/mir200c-(microrna-200c)

Historical Card

2011-08-01 MIR200C (microRNA 200c) by  Sarah Jurmeister,Stefan Uhlmann,Özgür Sahin 

Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Division of Molecular Genome Analysis, Im Neuenheimer Feld 580, Heidelberg, Germany