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MIR126 (microRNA 126)

Written2011-06Patrick Nana-Sinkam, Melissa Piper
Division of Pulmonary, Allergy, Critical Care, Sleep Medicine, College of Medicine, Davis Heart, Lung Research Institute Room 201, 473 W 12th Avenue, Columbus OH 43210, USA

(Note : for Links provided by Atlas : click)


Alias (NCBI)hsa-mir-126
microRNA 126
HGNC (Hugo) MIR126
HGNC Alias symbhsa-mir-126
HGNC Previous nameMIRN126
LocusID (NCBI) 406913
Atlas_Id 50387
Location 9q34.3  [Link to chromosome band 9q34]
Location_base_pair Starts at 136670602 and ends at 136670686 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping MIR126.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
Note The MiRNA126 are located in intron 7 of the epidermal growth factor (EGF)-like-domain, multiple 7 (EGFL7) gene. In addition, the antisense sequence to MIR126 within the hairpin pre-miRNA is also processed as a minor sequence miRNA, designated miRNA126*.


  Stem loop structure of MiR-126.
Description MiRNAs can be located within their own open reading frame (ORF) or within the intron of a host gene. Those miRNAs that are located within an intron are dependent on the transcriptional regulation of its host gene. In the human genome, miR-126 is found on chromosome 9 within intron 7 of the EGFL7 gene. An alternative miR-126 transcript from this region has also been reported and is designated miR-126*. Notably, EGFL7 expression is undetectable in normal brain tissue but is deregulated in malignant glioblastoma tumor cells as well as vascular endothelium cells within the tumor (Huang et al., 2010). EGFL7 is also secreted by endothelium and regulates angiogenesis. Recent studies demonstrate that both miR-126 and its host gene EGFL-7 harbor CpG islands invoking epigenetic regulation as one potential mechanism for the observed deregulation of miR-126 in both solid and hematologic malignancies (Saito et al., 2009).
Transcription MiRNAs are transcribed as a longer primary mRNA transcript which is called a pri-miR. The pri-miRs are processed mRNA molecules containing a 5' cap and a poly A tail and can range from hundred to thousand nucleotides (Nana-Sinkam et al., 2009). Currently the pri-miR for miR-126 is unknown. In the nucleus, the processing of the pri-miRs by the RNase enzyme, Drosha, to a smaller pre-miR molecule occurs (Nana-Sinkam et al., 2009). The pre-miR forms a stem loop structure to facilitate its transport to the nucleus. For miR-126, it is processed to an 85 nucleotide pre-miR that is then transported to the cytoplasm. Once in the cytoplasm, the pre-miR is incorporated in the RNA-inducible silencing complex (RISC). The RISC contains an RNase III endonuclease, Dicer, which further cleaves the pre-miR to the mature miRNA and minor antisense miRNA.
The mature sequence for miR-126 is 52-ucguaccgugaguaauaaugcg-73.

Minor miRNA sequence:
In some cases, the antisense sequence to the mature miRNA in the hairpin structure is also processed to a minor miRNA. A minor miRNA sequence has been identified for miR-126 and is designated MiR-126*.
- ID: hsa-miR-126*,
- miRBASE Accession #: MI0000444,
- Sequence: The mature sequence for miR-126* is 14-cauuauuacuuuugguacgcg-35.


Note MicroRNAs are not translated to protein.


Note No mutations have been identified.

Implicated in

Entity Various cancers
Note Deregulation of miR-126 has been described in several solid and hematologic malignancies including lung, prostate, breast, renal cell, cervical, thyroid cancers and Acute Leukemias. Furthermore, it has been implicated in regulating processes fundamental to tumor development and progression.
Entity Lung cancer: non-small cell cancer
Disease Several studies have demonstrated that miR-126 is reduced in lung cancer tissue compared to uninvolved adjacent lung tissue (Yanaihara et al., 2006).
Prognosis A recent study examining miR-126 expression in 335 lung cancer tissues revealed that elevated miR-126 along with VEGF were negative prognostic factors. Of note, miR-126 expression was of significant predictive value in squamous histology and in cases with lymphatic metastases (Donnem et al., 2011). A separate study identified up-regulation of miR-126 in metastatic sites of lung cancer (Barshack et al., 2010).
Therapeutic Implications: miR-126 represented one of a panel of miRNAs up-regulated in lung tumors from radiosensitive patients. Further investigation demonstrated that miR-126 could augment the apoptotic effects of irradiation in vitro (Wang et al., 2011).
Oncogenesis Tumor invasion and growth: miR-126 alters processes fundamental to tumor development and progression. In vitro gain of function reduced migratory and invasive capacity as well as proliferation. The CRK adapter protein, VEGF and the miR-126 host gene EGFL-7 are potential functional targets (Crawford et al., 2008; Liu et al., 2009).
Entity Lung cancer: small cell cancer
Oncogenesis MiR-126 gain of function in vitro reduced small cell cancer cell proliferation and induced G1 arrest (Miko et al., 2011).
Entity Colorectal carcinoma
Disease In a cohort of 66 colorectal carcinomas, miR-126 expression is reduced in colon cancer compared to 10 adjacent non tumor tissues (Li et al., 2010).
Oncogenesis MiR-126 has been shown to regulate the PI3-kinase signaling cascade through direct targeting of the p85beta subunit. This targeting resulted in an in vitro reduction in colon carcinoma cell growth (Guo et al., 2008).
Entity Breast cancer
Note Diagnostic: MiR-126 represented one of several miRNAs whose expression distinguished myoepithelial breast cancer from basal type breast cancer (Bockmeyer et al., 2011). A separate study suggested that miR-126 may serve as a non-invasive biomarker for breast cancer. Patients with breast cancer had lower circulating levels of miR-126 when compared to normal controls (Wang et al., 2010). Lastly, analysis for miR-126 single nucleotide polymorphisms (SNPs) in a cohort of 6042 patients did not identify an associated breast cancer risk (Wang et al., 2010).
Disease miR-126 has been shown to be down-regulated in breast cancer tissues.
Oncogenesis Tumor growth and Metastasis: In vitro, high metastatic breast cancer cell lines had lower levels of miR-126. MiR-126 gain of function reduced both breast cancer cell growth in vitro and metastases in vivo. Furthermore, miR-126 expression was inversely correlated with presence of metastases in a cohort of breast cancer patients (Tavazoie et al., 2008). Insulin Receptor Substrate (IRS-1) has been implicated as a functional target for miR-126 (Zhang et al., 2008).
Entity Gastric carcinoma
Prognosis In a cohort of 100 patients with gastric cancer miR-126 was one of a seven-miRNA signature that correlated with survival (Li et al., 2010).
Oncogenesis In vitro, miR-126 reduced gastric cancer cell proliferation (Otsubo et al., 2011; Feng et al., 2010). The transcriptional factor SOX2 has been suggested as one target.
Entity Renal cancer
Note Diagnostic: Early studies suggest that miR-126 expression may have diagnostic utility in renal carcinoma. In one study, miR-126 expression distinguished clear cell from renal cell carcinoma (Powers et al., 2011).
Entity Bladder cancer
Note Diagnostic: Investigators examined urinary miRNA expression patterns in a cohort of patients (N=36) and showed that the ratio of miR-126 to miR-152 could accurately diagnose bladder cancer with a specificity of 82% and sensitivity of 72% (Hanke et al., 2010).
Entity Leukemia
Note Diagnostic: Expression miRNA profiling in a cohort of 47 primary AML specimens followed by qPCR validation revealed that miR-126 and miR-126* could be used to distinguish subgroups of AML with highest expression occurring in core-binding factor (CBF) AML. Allied in vitro and in vivo studies demonstrated that miR-126 could induce proliferation of murine bone marrow progenitor cells in the presence of the AML1-ETO (AE) fusion gene (Li et al., 2008). The association between miR-126 and AML1/ETO rearrangements was further confirmed in a separate cohort of 29 AML samples (Cammarata et al., 2010). Low expression of miR-126 as part of a panel of miRNAs has been shown to correlate with CNS relapse in ALL (Zhang et al., 2009).


MicroRNA expression differentiates between primary lung tumors and metastases to the lung.
Barshack I, Lithwick-Yanai G, Afek A, Rosenblatt K, Tabibian-Keissar H, Zepeniuk M, Cohen L, Dan H, Zion O, Strenov Y, Polak-Charcon S, Perelman M.
Pathol Res Pract. 2010 Aug 15;206(8):578-84. Epub 2010 Apr 24.
PMID 20418022
MicroRNA profiles of healthy basal and luminal mammary epithelial cells are distinct and reflected in different breast cancer subtypes.
Bockmeyer CL, Christgen M, Muller M, Fischer S, Ahrens P, Langer F, Kreipe H, Lehmann U.
Breast Cancer Res Treat. 2011 Mar 17. [Epub ahead of print]
PMID 21409395
Differential expression of specific microRNA and their targets in acute myeloid leukemia.
Cammarata G, Augugliaro L, Salemi D, Agueli C, La Rosa M, Dagnino L, Civiletto G, Messana F, Marfia A, Bica MG, Cascio L, Floridia PM, Mineo AM, Russo M, Fabbiano F, Santoro A.
Am J Hematol. 2010 May;85(5):331-9.
PMID 20425795
MicroRNA-126 inhibits invasion in non-small cell lung carcinoma cell lines.
Crawford M, Brawner E, Batte K, Yu L, Hunter MG, Otterson GA, Nuovo G, Marsh CB, Nana-Sinkam SP.
Biochem Biophys Res Commun. 2008 Sep 5;373(4):607-12. Epub 2008 Jul 3.
PMID 18602365
Independent and tissue-specific prognostic impact of miR-126 in nonsmall cell lung cancer: Coexpression with vascular endothelial growth factor-A predicts poor survival.
Donnem T, Lonvik K, Eklo K, Berg T, Sorbye SW, Al-Shibli K, Al-Saad S, Andersen S, Stenvold H, Bremnes RM, Busund LT.
Cancer. 2011 Jul 15;117(14):3193-200. doi: 10.1002/cncr.25907. Epub 2011 Jan 24.
PMID 21264844
miR-126 functions as a tumour suppressor in human gastric cancer.
Feng R, Chen X, Yu Y, Su L, Yu B, Li J, Cai Q, Yan M, Liu B, Zhu Z.
Cancer Lett. 2010 Dec 1;298(1):50-63. Epub 2010 Jul 8.
PMID 20619534
Accurate molecular classification of renal tumors using microRNA expression.
Fridman E, Dotan Z, Barshack I, David MB, Dov A, Tabak S, Zion O, Benjamin S, Benjamin H, Kuker H, Avivi C, Rosenblatt K, Polak-Charcon S, Ramon J, Rosenfeld N, Spector Y.
J Mol Diagn. 2010 Sep;12(5):687-96. Epub 2010 Jul 1.
PMID 20595629
The noncoding RNA, miR-126, suppresses the growth of neoplastic cells by targeting phosphatidylinositol 3-kinase signaling and is frequently lost in colon cancers.
Guo C, Sah JF, Beard L, Willson JK, Markowitz SD, Guda K.
Genes Chromosomes Cancer. 2008 Nov;47(11):939-46.
PMID 18663744
A robust methodology to study urine microRNA as tumor marker: microRNA-126 and microRNA-182 are related to urinary bladder cancer.
Hanke M, Hoefig K, Merz H, Feller AC, Kausch I, Jocham D, Warnecke JM, Sczakiel G.
Urol Oncol. 2010 Nov-Dec;28(6):655-61. Epub 2009 Apr 17.
PMID 19375957
Expression and clinical significance of EGFL7 in malignant glioma.
Huang CH, Li XJ, Zhou YZ, Luo Y, Li C, Yuan XR.
J Cancer Res Clin Oncol. 2010 Nov;136(11):1737-43. Epub 2010 Mar 6.
PMID 20213100
Expression Profiling of Difficult-to-diagnose Thyroid Histologic Subtypes Shows Distinct Expression Profiles and Identify Candidate Diagnostic microRNAs.
Kitano M, Rahbari R, Patterson EE, Xiong Y, Prasad NB, Wang Y, Zeiger MA, Kebebew E.
Ann Surg Oncol. 2011 May 7. [Epub ahead of print]
PMID 21553140
Survival prediction of gastric cancer by a seven-microRNA signature.
Li X, Zhang Y, Zhang Y, Ding J, Wu K, Fan D.
Gut. 2010 May;59(5):579-85. Epub 2009 Nov 30.
PMID 19951901
Down-regulation of miR-126 expression in colorectal cancer and its clinical significance.
Li XM, Wang AM, Zhang J, Yi H.
Med Oncol. 2010 Jul 31. [Epub ahead of print]
PMID 20680522
Distinct microRNA expression profiles in acute myeloid leukemia with common translocations.
Li Z, Lu J, Sun M, Mi S, Zhang H, Luo RT, Chen P, Wang Y, Yan M, Qian Z, Neilly MB, Jin J, Zhang Y, Bohlander SK, Zhang DE, Larson RA, Le Beau MM, Thirman MJ, Golub TR, Rowley JD, Chen J.
Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15535-40. Epub 2008 Oct 1.
PMID 18832181
MiR-126 restoration down-regulate VEGF and inhibit the growth of lung cancer cell lines in vitro and in vivo.
Liu B, Peng XC, Zheng XL, Wang J, Qin YW.
Lung Cancer. 2009 Nov;66(2):169-75. Epub 2009 Feb 14.
PMID 19223090
miR-126 inhibits proliferation of small cell lung cancer cells by targeting SLC7A5.
Miko E, Margitai Z, Czimmerer Z, Varkonyi I, Dezso B, Lanyi A, Bacso Z, Scholtz B.
FEBS Lett. 2011 Apr 20;585(8):1191-6. Epub 2011 Mar 23.
PMID 21439283
Integrating the MicroRNome into the study of lung disease.
Nana-Sinkam SP, Hunter MG, Nuovo GJ, Schmittgen TD, Gelinas R, Galas D, Marsh CB.
Am J Respir Crit Care Med. 2009 Jan 1;179(1):4-10. Epub 2008 Sep 11. (REVIEW)
PMID 18787215
MicroRNA-126 inhibits SOX2 expression and contributes to gastric carcinogenesis.
Otsubo T, Akiyama Y, Hashimoto Y, Shimada S, Goto K, Yuasa Y.
PLoS One. 2011 Jan 27;6(1):e16617.
PMID 21304604
Molecular classification of adult renal epithelial neoplasms using microRNA expression and virtual karyotyping.
Powers MP, Alvarez K, Kim HJ, Monzon FA.
Diagn Mol Pathol. 2011 Jun;20(2):63-70.
PMID 21532496
Epigenetic therapy upregulates the tumor suppressor microRNA-126 and its host gene EGFL7 in human cancer cells.
Saito Y, Friedman JM, Chihara Y, Egger G, Chuang JC, Liang G.
Biochem Biophys Res Commun. 2009 Feb 13;379(3):726-31. Epub 2008 Dec 29.
PMID 19116145
miR-126 inhibits non-small cell lung cancer cells proliferation by targeting EGFL7.
Sun Y, Bai Y, Zhang F, Wang Y, Guo Y, Guo L.
Biochem Biophys Res Commun. 2010 Jan 15;391(3):1483-9. Epub 2009 Dec 24.
PMID 20034472
Endogenous human microRNAs that suppress breast cancer metastasis.
Tavazoie SF, Alarcon C, Oskarsson T, Padua D, Wang Q, Bos PD, Gerald WL, Massague J.
Nature. 2008 Jan 10;451(7175):147-52.
PMID 18185580
Correlation and quantitation of microRNA aberrant expression in tissues and sera from patients with breast tumor.
Wang F, Zheng Z, Guo J, Ding X.
Gynecol Oncol. 2010 Dec;119(3):586-93.
PMID 20801493
Expression and function of miRNA in postoperative radiotherapy sensitive and resistant patients of non-small cell lung cancer.
Wang XC, Du LQ, Tian LL, Wu HL, Jiang XY, Zhang H, Li DG, Wang YY, Wu HY, She Y, Liu QF, Fan FY, Meng AM.
Lung Cancer. 2011 Apr;72(1):92-9. Epub 2010 Aug 21.
PMID 20728239
Unique microRNA molecular profiles in lung cancer diagnosis and prognosis.
Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, Calin GA, Liu CG, Croce CM, Harris CC.
Cancer Cell. 2006 Mar;9(3):189-98.
PMID 16530703
Genetic variants within miR-126 and miR-335 are not associated with breast cancer risk.
Yang R, Dick M, Marme F, Schneeweiss A, Langheinz A, Hemminki K, Sutter C, Bugert P, Wappenschmidt B, Varon R, Schott S, Weber BH, Niederacher D, Arnold N, Meindl A, Bartram CR, Schmutzler RK, Muller H, Arndt V, Brenner H, Sohn C, Burwinkel B.
Breast Cancer Res Treat. 2011 Jun;127(2):549-54. Epub 2010 Nov 3.
PMID 21046227
MicroRNA patterns associated with clinical prognostic parameters and CNS relapse prediction in pediatric acute leukemia.
Zhang H, Luo XQ, Zhang P, Huang LB, Zheng YS, Wu J, Zhou H, Qu LH, Xu L, Chen YQ.
PLoS One. 2009 Nov 13;4(11):e7826.
PMID 19915715
The cell growth suppressor, mir-126, targets IRS-1.
Zhang J, Du YY, Lin YF, Chen YT, Yang L, Wang HJ, Ma D.
Biochem Biophys Res Commun. 2008 Dec 5;377(1):136-40. Epub 2008 Oct 1.
PMID 18834857
Endothelial-specific intron-derived miR-126 is down-regulated in human breast cancer and targets both VEGFA and PIK3R2.
Zhu N, Zhang D, Xie H, Zhou Z, Chen H, Hu T, Bai Y, Shen Y, Yuan W, Jing Q, Qin Y.
Mol Cell Biochem. 2011 May;351(1-2):157-64. Epub 2011 Jan 20.
PMID 21249429


This paper should be referenced as such :
Nana-Sinkam, P ; Piper, M
MIR126 (microRNA 126)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(12):1026-1029.
Free journal version : [ pdf ]   [ DOI ]

External links

HGNC (Hugo)MIR126   31508
Entrez_Gene (NCBI)MIR126    microRNA 126
AliasesMIRN126; miRNA126; mir-126
GeneCards (Weizmann)MIR126
Ensembl hg19 (Hinxton)ENSG00000199161 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000199161 [Gene_View]  ENSG00000199161 [Sequence]  chr9:136670602-136670686 [Contig_View]  MIR126 [Vega]
ICGC DataPortalENSG00000199161
TCGA cBioPortalMIR126
AceView (NCBI)MIR126
Genatlas (Paris)MIR126
SOURCE (Princeton)MIR126
Genetics Home Reference (NIH)MIR126
Genomic and cartography
GoldenPath hg38 (UCSC)MIR126  -     chr9:136670602-136670686 +  9q34.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)MIR126  -     9q34.3   [Description]    (hg19-Feb_2009)
GoldenPathMIR126 - 9q34.3 [CytoView hg19]  MIR126 - 9q34.3 [CytoView hg38]
Genome Data Viewer NCBIMIR126 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)LM608511
RefSeq transcript (Entrez)
Consensus coding sequences : CCDS (NCBI)MIR126
Gene ExpressionMIR126 [ NCBI-GEO ]   MIR126 [ EBI - ARRAY_EXPRESS ]   MIR126 [ SEEK ]   MIR126 [ MEM ]
Gene Expression Viewer (FireBrowse)MIR126 [ Firebrowse - Broad ]
GenevisibleExpression of MIR126 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)406913
GTEX Portal (Tissue expression)MIR126
Human Protein AtlasENSG00000199161-MIR126 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)MIR126
Human Protein Atlas [tissue]ENSG00000199161-MIR126 [tissue]
Protein Interaction databases
Ontologies - Pathways
PubMed336 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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