MIR26A1 (microRNA 26a-1)

2011-11-01   Bo Zhang , Qian Zhao 

Institute of Biochemistry, Cell Biology, Chinese Academy of Sciences, Shanghai, 200031, China (BZ); Department of Pathophysiology, Shanghai Jiao-Tong University, School of Medicine, Shanghai, 200030, China (QZ)

Identity

HGNC
LOCATION
3p22.2
LOCUSID
ALIAS
MIR26A,MIRN26A1,mir-26a-1

DNA/RNA

Note

The 22-bp precursor microRNA 26a-1 holds complete conservation among Human, Rhesus, Mouse and Dog. MIR26A1 functions as tumor suppressor gene in hepatocellular carcinoma (Ji et al., 2009; Kota et al., 2009), breast cancer (Zhang et al., 2011), rhabdomyosarcoma (Ciarapica et al., 2009) and MYC-induced lymphoma (Sander et al., 2008). Additionally, MIR26A1 potentially plays an important role in regulating IFN-β anti-inflammatory signaling (Witwer et al., 2010).
Atlas Image
The precursor MIR26A1 is composed of 77 nucleotides and its stem-loop structure is shown here. The sequence of mature MIR26A1 is marked in red.

Description

The precursor MIR26A1 maps on chromosome 3p22.2 spanning 77 bp and is located within one intron of CTDSPL (CTD (carboxy-terminal domain, RNA polymerase II, polypeptide A) small phosphatase-like, CTDSPL).

Transcription

The MIR26A1 gene is initially transcribed as a primary transcript in the nucleus and then further processed by the Drosha-Pasha/DGCR8 complex as an intermediate named the precursor microRNA 26a-1. After exported into cytoplasm by Exportin-5, the precursor microRNA 26a-1 was cleaved by Dicer as a duplex and in turn forms the mature 22-bp MIR26A1.

Mutations

Note

None.

Implicated in

Entity name
Hepatocellular carcinoma (HCC)
Note
MIR26A is reduced in hepatocellular carcinoma and directly suppresses the expression of ERα (estrogen receptor alpha, ERα) (Chen et al., 2011), cyclin D2 and cyclin E2 (Kota et al., 2009). The overexpression of MIR26A negatively regulates cell proliferation (Chen et al., 2011) and cell cycle (Kota et al., 2009). Systemic administration of MIR26A in a mouse model of HCC using adeno-associated virus (AAV) results in inhibition of cancer cell proliferation, induction of tumor-specific apoptosis, and dramatic protection from disease progression without toxicity (Kota et al., 2009).
Entity name
Nasopharyngeal carcinoma (NPC)
Note
MIR26A is commonly downregulated in NPC specimens and NPC cell lines and directly suppresses the expression of EZH2 (enhancer of zeste homolog 2, EZH2) (Lu et al., 2011). Ectopic expression of MIR26A inhibits growth and colony formation of NPC cells by inducing G1-phase cell-cycle arrest. MIR26A also suppresses tumorigenesis of NPC cells in vivo. MIR26A suppressed the expression of c-myc, cyclins D3 and E2, and cyclin-dependent kinases CDK4 and CDK6 while enhancing the expression of CDK inhibitors p14ARF and p21CIP1 in an EZH2-dependent manner.
Entity name
Breast cancer
Note
MIR26A is downregulated in breast cancer specimens and cell lines and directly regulates the expression of MTDH (metadherin, MTDH) and EZH2 (Zhang et al., 2011). MIR26A leads to apoptosis, inhibition of colony forming and in vivo tumorigenesis of breast cancer cells.
Entity name
Rhabdomyosarcoma
Note
In rhabdomyosarcoma, MIR26A is underexpressed while the mRNA of EZH2 is increased. EZH2 is one of direct targets of MIR26A in several different cell lines (Ciarapica et al., 2009; Lu et al., 2011; Zhang et al., 2011).
Entity name
Airway smooth muscle hypertrophy
Note
Stretch selectively induces the transcription of MIR26A in human airway smooth muscle cells (HASMCs). The transcription factor CCAAT enhancer-binding protein α (C/EBPα) directly activates miR-26a expression through the transcriptional machinery upon stretch. Glycogen synthase kinase-3β (GSK-3β) is a direct target of MIR26A (Mohamed et al., 2010). The enforced expression of MIR26A induces HASMC hypertrophy.
Entity name
Myogenesis
Note
MIR26A is up-regulated during myogenesis and directly targets EZH2. Overexpression of MIR26A in murine myogenic C2C12 cells induced creatine kinase activity. Moreover, myoD and myogenin mRNA expression levels were also up-regulated. Therefore, increased expression of miR-26a promotes myogenesis (Wong and Tellam, 2008).
Entity name
Osteogenic differentiation
Note
During hADSC (human adipose tissue-derived stem cells, hADSCs) differentiation, MIR26A shows increased expression. The inhibition of miR-26a increases protein levels of its predicted target, SMAD1 transcription factor (Luzi et al., 2008).

Bibliography

Pubmed IDLast YearTitleAuthors
216107002011Tumor-specific expression of microRNA-26a suppresses human hepatocellular carcinoma growth via cyclin-dependent and -independent pathways.Chen L et al
191066132009Deregulated expression of miR-26a and Ezh2 in rhabdomyosarcoma.Ciarapica R et al
198124002009MicroRNA expression, survival, and response to interferon in liver cancer.Ji J et al
195245052009Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model.Kota J et al
211998042011MiR-26a inhibits cell growth and tumorigenesis of nasopharyngeal carcinoma through repression of EZH2.Lu J et al
181977552008Osteogenic differentiation of human adipose tissue-derived stem cells is modulated by the miR-26a targeting of the SMAD1 transcription factor.Luzi E et al
205256812010Mechanical stretch up-regulates microRNA-26a and induces human airway smooth muscle hypertrophy by suppressing glycogen synthase kinase-3β.Mohamed JS et al
187139462008MYC stimulates EZH2 expression by repression of its negative regulator miR-26a.Sander S et al
201302132010MicroRNA regulation of IFN-beta protein expression: rapid and sensitive modulation of the innate immune response.Witwer KW et al
182812872008MicroRNA-26a targets the histone methyltransferase Enhancer of Zeste homolog 2 during myogenesis.Wong CF et al
209525132011Pathologically decreased miR-26a antagonizes apoptosis and facilitates carcinogenesis by targeting MTDH and EZH2 in breast cancer.Zhang B et al

Other Information

Locus ID:

NCBI: 407015
MIM: 612151
HGNC: 31610
Ensembl: ENSG00000199075
miRBase:

Variants:

dbSNP: 407015
ClinVar: 407015
TCGA: ENSG00000199075
COSMIC: MIR26A1

RNA/Proteins

Pathways

PathwaySourceExternal ID
MicroRNAs in cancerKEGGhsa05206
MicroRNAs in cancerKEGGko05206

References

Pubmed IDYearTitleCitations
211998042011MiR-26a inhibits cell growth and tumorigenesis of nasopharyngeal carcinoma through repression of EZH2.166
187139462008MYC stimulates EZH2 expression by repression of its negative regulator miR-26a.145
197011942009Zcchc11-dependent uridylation of microRNA directs cytokine expression.126
191389932008Genetic variations in microRNA-related genes are novel susceptibility loci for esophageal cancer risk.95
209525132011Pathologically decreased miR-26a antagonizes apoptosis and facilitates carcinogenesis by targeting MTDH and EZH2 in breast cancer.89
201302132010MicroRNA regulation of IFN-beta protein expression: rapid and sensitive modulation of the innate immune response.83
205256812010Mechanical stretch up-regulates microRNA-26a and induces human airway smooth muscle hypertrophy by suppressing glycogen synthase kinase-3β.73
242594262014MicroRNA-26a suppresses angiogenesis in human hepatocellular carcinoma by targeting hepatocyte growth factor-cMet pathway.73
235430602013MicroRNA-26 governs profibrillatory inward-rectifier potassium current changes in atrial fibrillation.71
228851552012MiR-26a enhances metastasis potential of lung cancer cells via AKT pathway by targeting PTEN.67

Citation

Bo Zhang ; Qian Zhao

MIR26A1 (microRNA 26a-1)

Atlas Genet Cytogenet Oncol Haematol. 2011-11-01

Online version: http://atlasgeneticsoncology.org/gene/51208/mir26a1