mir-210 microRNA

In molecular biology mir-210 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

mir-210
Conserved secondary structure of mir-210
Identifiers
Symbolmir-210
RfamRF00679
miRBase familyMIPF0000086
NCBI Gene406992
HGNC31587
OMIM612982
Other data
RNA typemicroRNA
Domain(s)Eukaryota; Chordata
PDB structuresPDBe

mir-210 has been strongly linked with the hypoxia pathway, and is upregulated in response to Hypoxia-inducible factors.[1] It is also overexpressed in cells affected by cardiac disease and tumours.[2] MiRNA-210 in particular, has been studied for its effects in rescuing cardiac function after myocardial infarcts via the up-regulation of angiogenesis and inhibition of cardiomyocyte apoptosis.[3]

Myocardial infarction therapy

Myocardial infarction is cardiac tissue necrosis that results from occlusion of blood supply via coronary arteries, thereby starving cells of oxygen and nutrients (termed ischemia). Prolong ischemia will eventually kill the cells and the destruction of cardiac cells leads to tissue death, which can lead to heart failure.

Delivery of miRNA-210 to an ischemic heart improves heart function, possibly by promoting the release of angiogenic factors like interleukin-1α (IL-1α), tumor necrosis factor-α (TNF-α) and leptin, as seen in HL-1 cardiomyocytes injected with miRNA-210.[3] However, miRNA-210 also targets the Efna3 and Ptp1b genes, which are genes which endogenously regulate angiogenesis and apoptosis, respectively.[3]

Ephrin-A3 (Efna3) is a gene that is involved in the inhibition of angiogenesis. Although it is known that Efna3 inhibits the formation of new blood vessels, its specific role is still unknown.[4] MiRNA-210 suppresses Efna3 at the mRNA level, thereby allowing angiogenesis to occur in cardiac tissue post-infarct.[3]

The second target gene, protein tyrosine phosphatase-1B (Ptp1b) is involved in the induction of apoptosis. Ptp1b gene protein has been known to regulate apoptosis by regulating the phosphorylation status of apoptotic proteins such as caspase-3 and caspase-8.[5] MiRNA-210 inhibits the effects of Ptp1b protein, which suppresses its pro-apoptotic functions.[3] Therefore, suppression of these two particular genes may contribute to the improvement of cardiac tissue and function by up-regulating angiogenesis and inhibiting apoptosis of cardiomyocytes after myocardial infarct.

Biomarker

Adrenocortical carcinoma

Mir-210 has been suggested as a useful biomarker to distinguish adrenocortical carcinoma from adrenocortical adenoma.[6]

Breast cancer

mir-210 expression is associated with survival in breast cancer. Higher expression indicates lower probability for survival in patients with breast cancer.[7]

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See also

References

  1. Huang X, Le QT, Giaccia AJ (May 2010). "MiR-210—micromanager of the hypoxia pathway". Trends in Molecular Medicine. 16 (5): 230–237. doi:10.1016/j.molmed.2010.03.004. PMC 3408219. PMID 20434954.
  2. Devlin C, Greco S, Martelli F, Ivan M (February 2011). "miR-210: More than a silent player in hypoxia". IUBMB Life. 63 (2): 94–100. doi:10.1002/iub.427. PMC 4497508. PMID 21360638.
  3. Hu S, Huang M, Li Z, Jia F, Ghosh Z, Lijkwan MA, Fasanaro P, Sun N, Wang X, Martelli F, Robbins RC, Wu JC (September 2010). "MicroRNA-210 as a novel therapy for treatment of ischemic heart disease". Circulation. 122 (11 Suppl): S124–31. doi:10.1161/circulationaha.109.928424. PMC 2952325. PMID 20837903.
  4. Fasanaro P, D'Alessandra Y, Di Stefano V, Melchionna R, Romani S, Pompilio G, Capogrossi MC, Martelli F (June 2008). "MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3". The Journal of Biological Chemistry. 283 (23): 15878–15883. doi:10.1074/jbc.m800731200. PMC 3259646. PMID 18417479.
  5. Song H, Zhang Z, Wang L (March 2008). "Small interference RNA against PTP-1B reduces hypoxia/reoxygenation induced apoptosis of rat cardiomyocytes". Apoptosis. 13 (3): 383–393. doi:10.1007/s10495-008-0181-1. PMID 18278556.
  6. Szabó DR, Luconi M, Szabó PM, Tóth M, Szücs N, Horányi J, Nagy Z, Mannelli M, Patócs A, Rácz K, Igaz P (March 2014). "Analysis of circulating microRNAs in adrenocortical tumors". Laboratory Investigation; A Journal of Technical Methods and Pathology. 94 (3): 331–339. doi:10.1038/labinvest.2013.148. PMID 24336071.
  7. Lánczky A, Nagy Á, Bottai G, Munkácsy G, Szabó A, Santarpia L, Győrffy B (December 2016). "miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients". Breast Cancer Research and Treatment. 160 (3): 439–446. doi:10.1007/s10549-016-4013-7. PMID 27744485.

Further reading

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