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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)

Identity

Alias_namesMIRN126
Alias_symbol (synonym)hsa-mir-126
Other aliasmicroRNA 126
miR-126
miRNA126
HGNC (Hugo) MIR126
LocusID (NCBI) 406913
Atlas_Id 50387
Location 9q34.3  [Link to chromosome band 9q34]
Location_base_pair Starts at 139565054 and ends at 139565138 bp from pter ( according to hg19-Feb_2009)  [Mapping MIR126.png]
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*.

DNA/RNA

 
  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.

Protein

Note MicroRNAs are not translated to protein.

Mutations

Note No mutations have been identified.

Implicated in

Note
  
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).
  

Bibliography

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Citation

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 ]
On line version : http://AtlasGeneticsOncology.org/Genes/MIR126ID50387ch9q34.html


External links

Nomenclature
HGNC (Hugo)MIR126   31508
Cards
AtlasMIR126ID50387ch9q34
Entrez_Gene (NCBI)MIR126  406913  microRNA 126
AliasesMIRN126; miRNA126; mir-126
GeneCards (Weizmann)MIR126
Ensembl hg19 (Hinxton)ENSG00000199161 [Gene_View]  chr9:139565054-139565138 [Contig_View]  MIR126 [Vega]
Ensembl hg38 (Hinxton)ENSG00000199161 [Gene_View]  chr9:139565054-139565138 [Contig_View]  MIR126 [Vega]
ICGC DataPortalENSG00000199161
TCGA cBioPortalMIR126
AceView (NCBI)MIR126
Genatlas (Paris)MIR126
WikiGenes406913
SOURCE (Princeton)MIR126
Genetics Home Reference (NIH)MIR126
miRBaseMIR126
dbDEMCMIR126
Genomic and cartography
GoldenPath hg19 (UCSC)MIR126  -     chr9:139565054-139565138 +  9q34.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)MIR126  -     9q34.3   [Description]    (hg38-Dec_2013)
EnsemblMIR126 - 9q34.3 [CytoView hg19]  MIR126 - 9q34.3 [CytoView hg38]
Mapping of homologs : NCBIMIR126 [Mapview hg19]  MIR126 [Mapview hg38]
OMIM611767   
Gene and transcription
Genbank (Entrez)LM608511
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)NC_000009 NC_018920 NT_008470 NW_004929369
Consensus coding sequences : CCDS (NCBI)MIR126
Alternative Splicing GalleryENSG00000199161
Gene ExpressionMIR126 [ NCBI-GEO ]   MIR126 [ EBI - ARRAY_EXPRESS ]   MIR126 [ SEEK ]   MIR126 [ MEM ]
Gene Expression Viewer (FireBrowse)MIR126 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)406913
GTEX Portal (Tissue expression)MIR126
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)MIR126
DMDM Disease mutations406913
Blocks (Seattle)MIR126
Human Protein AtlasENSG00000199161
Protein Interaction databases
FunCoupENSG00000199161
BioGRIDMIR126
STRING (EMBL)MIR126
ZODIACMIR126
Ontologies - Pathways
Huge Navigator MIR126 [HugePedia]
snp3D : Map Gene to Disease406913
BioCentury BCIQMIR126
ClinGenMIR126
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD406913
Chemical/Pharm GKB GenePA164722404
Clinical trialMIR126
Miscellaneous
canSAR (ICR)MIR126 (select the gene name)
Other databasemiRBase
Other databaseWikigenes
Probes
Litterature
PubMed140 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineMIR126
EVEXMIR126
GoPubMedMIR126
iHOPMIR126
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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