MIR126 (microRNA 126)

2011-06-01   Patrick 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

Identity

HGNC
LOCATION
9q34.3
LOCUSID
ALIAS
MIRN126,miRNA126,mir-126

DNA/RNA

Atlas Image
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 pre-miR sequence for miR-126 is 5-GCTGGCGACGGGACATTATTACTTTTGGTACGCGCTGTGACACTTCAAACTCGTACCGTGAGTAATAATGCGCCGTCCACGGCA-3.
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.

Proteins

Note

MicroRNAs are not translated to protein.

Implicated in

Entity name
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 name
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 name
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 name
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 name
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 name
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 name
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 name
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 name
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).

Bibliography

Pubmed IDLast YearTitleAuthors

Other Information

Locus ID:

NCBI: 406913
MIM: 611767
HGNC: 31508
Ensembl: ENSG00000199161
miRBase:

Variants:

dbSNP: 406913
ClinVar: 406913
TCGA: ENSG00000199161
COSMIC: MIR126

RNA/Proteins

Expression (GTEx)

0
1

Pathways

PathwaySourceExternal ID
MicroRNAs in cancerKEGGhsa05206
MicroRNAs in cancerKEGGko05206

References

Pubmed IDYearTitleCitations
378644822024MicroRNA-30d and -483-3p for bi-ventricular remodelling and miR-126-3p for pulmonary hypertension in advanced heart failure.2
380088592024Low circulating levels of miR-17 and miR-126-3p are associated with increased mortality risk in geriatric hospitalized patients affected by cardiovascular multimorbidity.0
381658522024Genetic variants rs2910164, rs4636297 and rs895819 may contribute to the onset of acute myocardial infarction in Pakistani population.0
382812932024Association of ATG10 rs1864183, ATG16L1 rs2241880 and miR-126 with esophageal cancer.0
384454622024Methylation Status of miR-34a and miR-126 in Non-Small Cell Lung Cancer (NSCLC) Tumor Tissues.1
384879202024miR-107 and miR-126 and Risk of Breast Cancer: A Case-Control Study.0
388396662024Urinary extracellular vesicle-derived miR-126-3p predicts lymph node invasion in patients with high-risk prostate cancer.0
390085222024Exosomal miR-126-3p: Potential protection against vascular damage by regulating the SLC7A5/mTOR Signalling pathway in human umbilical vein endothelial cells.0
378644822024MicroRNA-30d and -483-3p for bi-ventricular remodelling and miR-126-3p for pulmonary hypertension in advanced heart failure.2
380088592024Low circulating levels of miR-17 and miR-126-3p are associated with increased mortality risk in geriatric hospitalized patients affected by cardiovascular multimorbidity.0
381658522024Genetic variants rs2910164, rs4636297 and rs895819 may contribute to the onset of acute myocardial infarction in Pakistani population.0
382812932024Association of ATG10 rs1864183, ATG16L1 rs2241880 and miR-126 with esophageal cancer.0
384454622024Methylation Status of miR-34a and miR-126 in Non-Small Cell Lung Cancer (NSCLC) Tumor Tissues.1
384879202024miR-107 and miR-126 and Risk of Breast Cancer: A Case-Control Study.0
388396662024Urinary extracellular vesicle-derived miR-126-3p predicts lymph node invasion in patients with high-risk prostate cancer.0

Citation

Patrick Nana-Sinkam ; Melissa Piper

MIR126 (microRNA 126)

Atlas Genet Cytogenet Oncol Haematol. 2011-06-01

Online version: http://atlasgeneticsoncology.org/gene/50387/gene-fusions-explorer/img/logo-atlas-4.svg