Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India; firstname.lastname@example.org
Review on CCND1, with data on DNA, on the protein encoded, and where the gene is implicated.
in Gastric cancer cell line BGC-823
Binds to 3 UTR of CCND1 in gastric cancer. miR-365 markedly decreased the expression (mRNA and protein) of CCND1. Conversely, miR365 knockdown repressed cell growth, which can be overcome by CCND1 over-expression. Similar inverse co-relation was obtained between miR-365 and CCND1 expression in patient samples. (Long-Guo et. al., 2013).
in Vascular smooth muscle cell (VSMC)
miR-365 suppresses CCND1 significantly in mRNA and protein levels in primary rat VSMC. CCND1 is a direct target of miR-365 in vascular smooth muscle cells, as shown by significant inhibition of the luciferase activity of wild type CCND1 3 UTR, but not the mutant cyclinD1 3 UTR with the mutant biding site of miR-365 (Zhang et. al., 2014). CCND1 is a potential target of mir-365 through direct binding. (Kim et. al., 2014).
in Colon cancer
miRNA directly binds to the 3UTR of CCND1, proved by luciferase reporter assay. Transfection of miR365 significantly decreased CCND1 expression in HT29 and LoVo cells. Pearsons co-relation between miR-365 levels and CCND1 expression by qRT-PCR and western blot showed that they were inversely correlated (Nie et. al., 2012).
miR-338-3p in Hepatocyte cell line LO2
miR-338-3p binds at two regions in the 3 UTR of CCND1( mainly at the site spanning nucleotides 2397-2403). Overexpression of miR-338-3p downregulates endogenous CyclinD1 protein, while inhibition upregulates CyclinD1 protein, without any change in CCND1 mRNA levels. miR-338-3p post-transcriptionally regulates CCND1 (Fu et. al., 2012).
miR-19a in Human umbilical vein endothelial cells (HUVECs)
miR-19a binding site (nucleotides 1,778-1,785 in human CCND1) identified by sequence alignment, which is highly conserved among different species. Binding of miR-19a to 3 UTR of CCND1 verified by luciferase assay. CCND1 protein expression markedly reduced upon over-expression of miR-19a, although no change in RNA expression. miR-19a post-transcriptionally regulates CCND1 expression (Qin et. al., 2010).
miR-490-3p in A549 Lung cancer cell line
miR-490-3p binds to 3 UTR of CCND1. Over-expression decreased the expression of CCND1, both at the RNA and protein levels (Gu et. al., 2014).
miR-302 in Endometrial cell line Ishikawa
Directly targets CCND1 and significantly inhibited protein expression (Yan et. al., 2014).
miR-449-a in Gastric cancer cell line SGC7901
miR-449a inhibited SGC7901 cells proliferation and enhanced cisplatin chemosensitivity by downregulating expression of CCND1, respectively, via directly targeting the 3-untranslated regions of CCND1 mRNA (Hu et. al., 2014).
miR-16 in Bladder cancer cell line TCHu-1
Binding of miR16 to 3 UTR of CCND1 and its reduced expression was validated by luciferase assay, while the reverse result was obtained by mutation of the conserved miR-16 binding motif. Overexpression of miR-16 in TCHu-1 cells led to reduced CCND1 protein expression, whereas its inhibition led to an increased expression of CCND1 (Jiang et. al., 2013).
miR-9 in Gastric cancer
Databases indicated potential binding site of miR-9 with high complementarity at CCND1 39-UTR (bases 2974-2995), which was validated by luciferase reporter assay. Significant inverse correlation between miR-9 expression and CCND1 transcript levels in gastric cancer tissues and cell lines. Overexpression of miR9 in gastric cancer cell lines SGC-7901 and AGS resulted in reduced RNA and protein expression of CCND1, whereas knockdown of miR-9 produced the opposite result, proving that miR-9 considerably inhibited the expression of CCND1 through post-transcriptional repression. Results validated by in-vitro experiments (Zheng et. al., 2013).
miR-195 in Glioma
Analysis using publicly available algorithms (TargetScan, Pictar, miRANDA) indicates that CCND1 is a predicted target of miR-195, which was validated by overexpression of miR- 195, which reduced, but inhibition of miR-195 increased, the luciferase activity of CCND1-39UTR in a consistent and dose-dependent manner. Upregulation of miR-195 decreased, but inhibition of miR-195 increased, the expression levels of CCND1 in LN18 and T98G glioma cells. The findings were also validated in a model system in mice (Hui et. al., 2013).
miR-155 in Human extravillous trophoblast derived HTR-8/SVneo cells
Bioinformatics analysis showed that, at the 3 untranslated region (UTR) of CCND1, six bases are complementary to the seed region of miR-155. Luciferase assays and CCND1 3UTR transfection assays validated that CCND1 3UTR was the target of miR-155 in HTR-8/SVneo cells. Overexpression of miR-155 in HTR-8/SVneo cells reduced the level of CCND1 protein (Dai et. al., 2012).
miR-143 in Mesenchymal stem cells from the bone marrow of male Fischer 344 rats
Ectopic expression of miR-143 also increased CCND1 in the native MSC as compared with scramble transfected cells .On the contrary, pre-treatment of AAMSC with miR-143 specific antagomir significantly abolished CCND1 expression (Lai et. al., 2012).
in Mouse liver regeneration
Cyclin D expression and G1 phase transition of hepatocytes after 2/3 PH depend on induced miR-21 expression. Knockdown of miR-21 impaired progression of hepatocytes into S phase of the cell cycle, mainly through a decrease in levels of cyclinD1 protein, but not Ccnd1 mRNA, whereas increased miR-21 expression facilitated CCND1 translation in the early phase of liver regeneration (Ng et. al., 2012).
in Renal cancer
miR-21 controlled the expression of CCND1 through NF?B-dependent transcription and mediated renal cancer cell proliferation by CCND1 (Bera et. al., 2013).
miR-520-b in Hepatoma cell lines
miR520-b directly targets the 3 UTR of CCND1; proved by dual luciferase reporter system. Down-regulation of protein levels of CCND1 occurred on over-expression of miR520-b in HepG2 and H7402 cells, while the over-expression occurred on inhibition in miR520-b. Tumors in mice over-expressing miR520-b also showed lower CCND1 expression (Zhang et. al., 2012).
miR-193b in Melanoma
TargetScan showed that miR193b binds to the 3UTR of CCND1, which was proved by luciferase reporter assay. miR-193b over-expression led to nearly 50% reduction in CCND1 mRNA and protein levels in Malme-3M cells than in control (Chen et. al., 2010).
miR-17/20 in Breast cancer
Levels of the miR-17-5p/miR-20a miRNA cluster were inversely correlated to CCND1 abundance in human breast tumors and cell lines. miR 17/20 negatively regulates the expression of CCND1 by binding to a conserved 3UTR region (nucleotides 2,109-2,117) of the gene (Yu et. al., 2008).
miR-20 and miR106-a in Spermatogonial stem cells (SCC)
They promote renewal at the post-transcriptional level via targeting CCND1. Knockdown of CCND1 results in renewal of SCCs (He et. al., 2013).
miR-503 in Endometrioid endometrial cancer (EEC)
Binds to 5 UTR of CCND1 and its expression is inversely co-related with CCND1 in EEC tissues and cell lines (Xu et. al., 2013).
miR-449b in SW116 colon cancer stem cell
Transfecting pre-miR-449b and inhibiting miR-449b altered protein expression levels of CCND1 (Fang, 2013).
miR-15a and miR16-1 in Osteosarcoma
They bind to 3-UTR of CCND1 and suppress transcription of CCND1 (Cai et. al., 2012).
miR-138 in Nasopharyngeal carcinoma
CCND1 is a novel direct target of miR138. mRNA levels of CCND1 were inversely correlated with miR-138 expression (Liu et. al., 2012).
miR-34a in A549 cell line
Ectopic expression of miR-34a reduces both mRNA and protein levels of CCND1 by targeting the 3-untranslated mRNA region of CCND1 (Sun et. al., 2008).
miR-29a in Breast cancer cell lines
Over-expression of miR29a down-regulation of CCND1 expression in MDA-MB-453 cells, whereas in MCF-10A cells with Mir-29a knockdown, CCND1 was up-regulated (Wu et. al., 2013).
miR-7 in Colorectal cancer cell lines
Over-expression of miR-7 significantly decreased CCND1 expression (Xu et. al., 2014).
miR-545 in Lung cancer
miR-545 caused cell cycle arrest at the G0/G1 phase and induced cell apoptosis in lung cancer cells by targeting CCND1. The effects of CCND1 down-regulated by miR-545 were similar to those caused by siRNAs of CCND1 and over-expression of CCND1 could abolish the miR-545-induced inhibition of cell proliferation (Du et. al., 2014).
miR-125b in Melanoma
Cells over-expressing miR-125b exhibited reduced expression of CCND1 (Nyholm et. al., 2014).
miR-147 in Colon and lung cancer cells.
Transfection of miR147 led to down-regulation of CCND1 (Lee et. al., 2014).
CCND1 was more frequently up-regulated in mammary tumors from transgenic mice (expressing myristoylated-Akt1 (myr-Akt1) under the control of the MMTV-LTR promoter) compared to tumors from wild-type mice. Increased expression of CCND1 was incompletely dependent on Akt1 expression. Low expression of CCND1 and increased expression of Twist and Slug was observed in mammary tumors that had metastasized to secondary sites (Wu et. al., 2014).
Embelin-treated mice showed significant inhibition in tumor growth, which was associated with reduced expression of CCND1 (Huang et. al., 2014).
Nicotine significantly increased expression of CCND1 (He et. al., 2014).
In mice treated with hUCMSCs-LV-IL-21, Expression of cyclin-D1 was simultaneously low compared to control group, hUCMSCs group and hUCMSCs-LV-Vec group (Zhang et. al., 2014).
Dairy Cow Mammary Epithelial Cells:
Treatment with leucine induced LeuRS, increasing CCND1 mRNA and protein expression (Wang et. al., 2014).
CCND1 accumulation due to differential effects of of PKC? and PKC? was likely contribute to the opposing tumor suppressive and tumor promoting activities in the intestinal epithelium (Pyfz et. al., 2014).
IGF-1R activation together with EGFR co-signaling decreased the percentage of cells in G1 and enhanced cell progression into S and G2 by increases in expression of CCND1 (Alagappan et. al., 2014).
CCND1 mRNA was significantly decreased by sodium ferulate in cells under serum stimulation (Zhang et. al., 2014).
Sophocarpine inhibited the proliferation of HSCs by a decrease in the expression of CCND1 (Qian et. al., 2014).
Rat Airway Smooth Muscle Cells:
Increased CCND1 expression during acceleration of cell cycle at G1/ S phase in CMF was due to CARP (cardiac ankyrin repeat protein) over-expression (Ma. et. al., 2014).
Shreya Sarkar ; Chinmay Kumar Panda
CCND1 (B-cell leukemia/lymphoma 1)
Atlas Genet Cytogenet Oncol Haematol. 2015-04-01
Online version: http://atlasgeneticsoncology.org/gene/36/bcl1id36
1998-05-01 CCND1 (B-cell leukemia/lymphoma 1) by Jean-Loup Huret