“Mir-22”的意思、由来-开放百科全书

In molecular biology mir-22 microRNA is a short RNA molecule. MicroRNAs are an abundant class of molecules, approximately 22 nucleotides in length, which can post-transcriptionally regulate gene expression by binding to the 3' UTR of mRNAs expressed in a cell.

Origins

Mir-22 was originally identified in HeLa cells (an immortal cell line derived from cervical cancer cells), but was later found to be ubiquitously expressed in various tissues.^[1] The gene encoding miR-22 is found on the short arm of chromosome 17, in a minimal loss of heterozygosity region. It is highly conserved across many vertebrate species, including chimp, mouse, rat, dog and horse. This level of conservation suggests functional importance. MiR-22 was previously identified as having a role in erythrocyte maturation.^[2]

Role in cancer

The deregulation of many miRNAs has been shown to have a role in oncogenesis. Mir-22 was found to be over-expressed in prostate cancer but down-regulated in breast cancer, cholangiocarcinoma, multiple myeloma and hepatocellular carcinoma.^[3] Mir-22 expression was associated with survival in multiple breast cancer datasets.^[4]

Targets

Specifically, miR-22 can function as a tumour suppressor. One known target is histone deacetylase 4 (HDAC4), which is known to have a critical role in cancer development. Mir-22 also targets Myc Binding Protein (MYCBP).^[5] This prevents transcription of c-Myc target genes by silencing c-MYCBP. However, c-Myc also inhibits expression of miR-22 in a positive feedback loop. When this spirals out of control, it can cause uncontrolled cell proliferation.^[6]

Possible therapy

Expression of miR-22 can be induced by adding 12-O-Tetradecanoylphorbol-13-acetate (TPA) to HL-60 cells (leukaemia cell line).^[7] The enforced expression causes the growth of cancer cells to slow down. This means that miR-22 could be a potential target for cancer therapies.

See also

References

1. ^{{cite journal |vauthors=Xiong J, Yu D, Wei N, Fu H, Cai T, Huang Y, Wu C, Zheng X, Du Q, Lin D, Liang Z |title=An estrogen receptor alpha suppressor, microRNA-22, is downregulated in estrogen receptor alpha-positive human breast cancer cell lines and clinical samples. |journal=FEBS J |volume=277 |issue=7 |pages=1684–94 |year=2010 |pmid=20180843 |doi=10.1111/j.1742-4658.2010.07594.x}}
2. ^{{cite journal |vauthors=Choong ML, Yang HH, McNiece I |title=MicroRNA expression profiling during human cord blood-derived CD34 cell erythropoiesis |journal=Exp. Hematol. |volume=35 |issue=4 |pages=551–64 |date=April 2007 |pmid=17379065 |doi=10.1016/j.exphem.2006.12.002 |url=}}
3. ^{{cite journal |vauthors=Zhang J, Yang Y, Yang T, Liu Y, Li A, Fu S, Wu M, Pan Z, Zhou W |title=microRNA-22, downregulated in hepatocellular carcinoma and correlated with prognosis, suppresses cell proliferation and tumourigenicity |journal=Br J Cancer |volume=103 |issue=8 |pages=1215–20 |year=2010 |pmid=20842113 |doi=10.1038/sj.bjc.6605895 |pmc=2967065}}
4. ^{{Cite journal|last=Lánczky|first=András|last2=Nagy|first2=Ádám|last3=Bottai|first3=Giulia|last4=Munkácsy|first4=Gyöngyi|last5=Szabó|first5=András|last6=Santarpia|first6=Libero|last7=Győrffy|first7=Balázs|date=2016-12-01|title=miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients|journal=Breast Cancer Research and Treatment|volume=160|issue=3|pages=439–446|doi=10.1007/s10549-016-4013-7|issn=1573-7217|pmid=27744485}}
5. ^{{cite journal |vauthors=Xiong J, Du Q, Liang Z |title=Tumor-suppressive microRNA-22 inhibits the transcription of E-box-containing c-Myc target genes by silencing c-Myc binding protein |journal=Oncogene |volume=29 |issue=35 |pages=4980–8 |year=2010 |pmid=20562918 |doi=10.1038/onc.2010.241}}
6. ^{{cite journal |vauthors=Cole MD, McMahon SB |title=The Myc oncoprotein: a critical evaluation of transactivation and target gene regulation |journal=Oncogene |volume=18 |issue=19 |pages=2916–24 |date=May 1999 |pmid=10378688 |doi=10.1038/sj.onc.1202748 |url=}}
7. ^{{cite journal |vauthors=Ting Y, Medina DJ, Strair RK, Schaar DG |title=Differentiation-associated miR-22 represses Max expression and inhibits cell cycle progression |journal=Biochem Biophys Res Commun |volume=394 |issue=3 |pages=606–11 |year=2010 |pmid=20214878 |doi=10.1016/j.bbrc.2010.03.030}}