Mir-210 microRNA explained

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 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. However, miRNA-210 also targets the Efna3 and Ptp1b genes, which are genes which endogenously regulate angiogenesis and apoptosis, respectively.

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.

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. 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]

See also

• MicroRNA

Further reading

• Tsuchiya S, Fujiwara T, Sato F, Shimada Y, Tanaka E, Sakai Y, Shimizu K, Tsujimoto G . MicroRNA-210 regulates cancer cell proliferation through targeting fibroblast growth factor receptor-like 1 (FGFRL1) . The Journal of Biological Chemistry . 286 . 1 . 420–428 . January 2011 . 21044961 . 3013001 . 10.1074/jbc.M110.170852 . free .
• Li T, Cao H, Zhuang J, Wan J, Guan M, Yu B, Li X, Zhang W . Identification of miR-130a, miR-27b and miR-210 as serum biomarkers for atherosclerosis obliterans . Clinica Chimica Acta; International Journal of Clinical Chemistry . 412 . 1–2 . 66–70 . January 2011 . 20888330 . 10.1016/j.cca.2010.09.029 .
• Puisségur MP, Mazure NM, Bertero T, Pradelli L, Grosso S, Robbe-Sermesant K, Maurin T, Lebrigand K, Cardinaud B, Hofman V, Fourre S, Magnone V, Ricci JE, Pouysségur J, Gounon P, Hofman P, Barbry P, Mari B . miR-210 is overexpressed in late stages of lung cancer and mediates mitochondrial alterations associated with modulation of HIF-1 activity . Cell Death and Differentiation . 18 . 3 . 465–478 . March 2011 . 20885442 . 3131992 . 10.1038/cdd.2010.119 .
• Hu S, Huang M, Li Z, Jia F, Ghosh Z, Lijkwan MA, Fasanaro P, Sun N, Wang X, Martelli F, Robbins RC, Wu JC . MicroRNA-210 as a novel therapy for treatment of ischemic heart disease . Circulation . 122 . 11 Suppl . S124–31 . September 2010 . 20837903 . 2952325 . 10.1161/CIRCULATIONAHA.109.928424 .
• Zhang GL, Li YX, Zheng SQ, Liu M, Li X, Tang H . Suppression of hepatitis B virus replication by microRNA-199a-3p and microRNA-210 . Antiviral Research . 88 . 2 . 169–175 . November 2010 . 20728471 . 10.1016/j.antiviral.2010.08.008 .
• Chen Z, Li Y, Zhang H, Huang P, Luthra R . Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression . Oncogene . 29 . 30 . 4362–4368 . July 2010 . 20498629 . 10.1038/onc.2010.193 .
• Favaro E, Ramachandran A, McCormick R, Gee H, Blancher C, Crosby M, Devlin C, Blick C, Buffa F, Li JL, Vojnovic B, Pires das Neves R, Glazer P, Iborra F, Ivan M, Ragoussis J, Harris AL . MicroRNA-210 regulates mitochondrial free radical response to hypoxia and krebs cycle in cancer cells by targeting iron sulfur cluster protein ISCU . PLOS ONE . 5 . 4 . e10345 . April 2010 . 20436681 . 2859946 . 10.1371/journal.pone.0010345 . Gartel . Andrei L. . 2010PLoSO...510345F . free .
• Ho AS, Huang X, Cao H, Christman-Skieller C, Bennewith K, Le QT, Koong AC . Circulating miR-210 as a Novel Hypoxia Marker in Pancreatic Cancer . Translational Oncology . 3 . 2 . 109–113 . April 2010 . 20360935 . 2847318 . 10.1593/tlo.09256 .
• Chan SY, Loscalzo J . MicroRNA-210: a unique and pleiotropic hypoxamir . Cell Cycle . 9 . 6 . 1072–1083 . March 2010 . 20237418 . 2912143 . 10.4161/cc.9.6.11006 .
• Gee HE, Camps C, Buffa FM, Patiar S, Winter SC, Betts G, Homer J, Corbridge R, Cox G, West CM, Ragoussis J, Harris AL . hsa-mir-210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer . Cancer . 116 . 9 . 2148–2158 . May 2010 . 20187102 . 10.1002/cncr.25009 . 29964899 . free .
• Kushibiki T . Photodynamic therapy induces microRNA-210 and -296 expression in HeLa cells . Journal of Biophotonics . 3 . 5–6 . 368–372 . June 2010 . 19953537 . 10.1002/jbio.200900082 .
• Fasanaro P, Greco S, Lorenzi M, Pescatori M, Brioschi M, Kulshreshtha R, Banfi C, Stubbs A, Calin GA, Ivan M, Capogrossi MC, Martelli F . An integrated approach for experimental target identification of hypoxia-induced miR-210 . The Journal of Biological Chemistry . 284 . 50 . 35134–35143 . December 2009 . 19826008 . 2787374 . 10.1074/jbc.M109.052779 . free .
• Chan SY, Zhang YY, Hemann C, Mahoney CE, Zweier JL, Loscalzo J . MicroRNA-210 controls mitochondrial metabolism during hypoxia by repressing the iron-sulfur cluster assembly proteins ISCU1/2 . Cell Metabolism . 10 . 4 . 273–284 . October 2009 . 19808020 . 2759401 . 10.1016/j.cmet.2009.08.015 .
• Huang X, Ding L, Bennewith KL, Tong RT, Welford SM, Ang KK, Story M, Le QT, Giaccia AJ . Hypoxia-inducible mir-210 regulates normoxic gene expression involved in tumor initiation . Molecular Cell . 35 . 6 . 856–867 . September 2009 . 19782034 . 2782615 . 10.1016/j.molcel.2009.09.006 .
• Mathew LK, Simon MC . mir-210: a sensor for hypoxic stress during tumorigenesis . Molecular Cell . 35 . 6 . 737–738 . September 2009 . 19782023 . 2869244 . 10.1016/j.molcel.2009.09.008 .
• Kim HW, Haider HK, Jiang S, Ashraf M . Ischemic preconditioning augments survival of stem cells via miR-210 expression by targeting caspase-8-associated protein 2 . The Journal of Biological Chemistry . 284 . 48 . 33161–33168 . November 2009 . 19721136 . 2785158 . 10.1074/jbc.M109.020925 . free .
• Bianchi N, Zuccato C, Lampronti I, Borgatti M, Gambari R . Expression of miR-210 during erythroid differentiation and induction of gamma-globin gene expression . BMB Reports . 42 . 8 . 493–499 . August 2009 . 19712585 . 10.5483/BMBRep.2009.42.8.493 . free .
• Zhang Z, Sun H, Dai H, Walsh RM, Imakura M, Schelter J, Burchard J, Dai X, Chang AN, Diaz RL, Marszalek JR, Bartz SR, Carleton M, Cleary MA, Linsley PS, Grandori C . MicroRNA miR-210 modulates cellular response to hypoxia through the MYC antagonist MNT . Cell Cycle . 8 . 17 . 2756–2768 . September 2009 . 19652553 . 10.4161/cc.8.17.9387 . free .
• Mizuno Y, Tokuzawa Y, Ninomiya Y, Yagi K, Yatsuka-Kanesaki Y, Suda T, Fukuda T, Katagiri T, Kondoh Y, Amemiya T, Tashiro H, Okazaki Y . miR-210 promotes osteoblastic differentiation through inhibition of AcvR1b . FEBS Letters . 583 . 13 . 2263–2268 . July 2009 . 19520079 . 10.1016/j.febslet.2009.06.006 . free .
• Pulkkinen K, Malm T, Turunen M, Koistinaho J, Ylä-Herttuala S . Hypoxia induces microRNA miR-210 in vitro and in vivo ephrin-A3 and neuronal pentraxin 1 are potentially regulated by miR-210 . FEBS Letters . 582 . 16 . 2397–2401 . July 2008 . 18539147 . 10.1016/j.febslet.2008.05.048 . free .
• Fasanaro P, D'Alessandra Y, Di Stefano V, Melchionna R, Romani S, Pompilio G, Capogrossi MC, Martelli F . 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 . June 2008 . 18417479 . 3259646 . 10.1074/jbc.M800731200 . free .
• Corn PG . Hypoxic regulation of miR-210: shrinking targets expand HIF-1's influence . Cancer Biology & Therapy . 7 . 2 . 265–267 . February 2008 . 18347426 . 10.4161/cbt.7.2.5745 . free .
• Camps C, Buffa FM, Colella S, Moore J, Sotiriou C, Sheldon H, Harris AL, Gleadle JM, Ragoussis J . hsa-miR-210 Is induced by hypoxia and is an independent prognostic factor in breast cancer . Clinical Cancer Research . 14 . 5 . 1340–1348 . March 2008 . 18316553 . 10.1158/1078-0432.CCR-07-1755 . free .
• Giannakakis A, Sandaltzopoulos R, Greshock J, Liang S, Huang J, Hasegawa K, Li C, O'Brien-Jenkins A, Katsaros D, Weber BL, Simon C, Coukos G, Zhang L . miR-210 links hypoxia with cell cycle regulation and is deleted in human epithelial ovarian cancer . Cancer Biology & Therapy . 7 . 2 . 255–264 . February 2008 . 18059191 . 3233968 . 10.4161/cbt.7.2.5297 .

Notes and References

1. Huang X, Le QT, Giaccia AJ . MiR-210—micromanager of the hypoxia pathway . Trends in Molecular Medicine . 16 . 5 . 230–237 . May 2010 . 20434954 . 3408219 . 10.1016/j.molmed.2010.03.004 .
2. Devlin C, Greco S, Martelli F, Ivan M . miR-210: More than a silent player in hypoxia . IUBMB Life . 63 . 2 . 94–100 . February 2011 . 21360638 . 4497508 . 10.1002/iub.427 .
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 . MicroRNA-210 as a novel therapy for treatment of ischemic heart disease . Circulation . 122 . 11 Suppl . S124–31 . September 2010 . 20837903 . 2952325 . 10.1161/circulationaha.109.928424 .
4. Fasanaro P, D'Alessandra Y, Di Stefano V, Melchionna R, Romani S, Pompilio G, Capogrossi MC, Martelli F . 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 . June 2008 . 18417479 . 3259646 . 10.1074/jbc.m800731200 . free .
5. Song H, Zhang Z, Wang L . Small interference RNA against PTP-1B reduces hypoxia/reoxygenation induced apoptosis of rat cardiomyocytes . Apoptosis . 13 . 3 . 383–393 . March 2008 . 18278556 . 10.1007/s10495-008-0181-1 . 32666751 .
6. Szabó DR, Luconi M, Szabó PM, Tóth M, Szücs N, Horányi J, Nagy Z, Mannelli M, Patócs A, Rácz K, Igaz P . Analysis of circulating microRNAs in adrenocortical tumors . Laboratory Investigation; A Journal of Technical Methods and Pathology . 94 . 3 . 331–339 . March 2014 . 24336071 . 10.1038/labinvest.2013.148 . free .
7. Lánczky A, Nagy Á, Bottai G, Munkácsy G, Szabó A, Santarpia L, Győrffy B . 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 . December 2016 . 10.1007/s10549-016-4013-7 . 27744485 . 11165696 .