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In molecular biology miR-375 microRNA is a short RNA molecule. MicroRNAs (miRNAs) are small (18-25 nucleotides), non-coding RNAs that regulate genes post-transcriptionally by inhibiting translation and/or causing mRNA degradation. miR-375 is found on human chromosome 2 in between the CRYBA2 and CCDC108 genes.
miR-375 is specifically expressed in the pancreatic islets and brain. miR-375 was one of the first miRNAs identified in the pancreas (Poy et al, 2004), and remains one of the best characterised in terms of function. It is expressed in the pancreas and pituitary gland, organs linked by their role in hormone secretion, and expression levels increase during pancreas organogenesis. Loss-of-function studies showed that miR-375 is essential for β-cell formation in zebrafish (Kloosterman et al, 2007). miR-375 knockout mice have decreased numbers of β-cells and increased numbers of α-cells. The increase in glucagon levels, combined with the reduction in insulin levels, results in hyperglycaemia. This shows the importance of miR-375 in the establishment of normal pancreatic cell mass through the targeting of a group of genes which control cellular growth and proliferation in the developing pancreas (Poy et al, 2009). Further evidence for the involvement of miR-375 in pancreas development includes the fact that its expression is regulated by several transcription factors important in pancreatic development and function, including HNF6, INSM1, NGN3, NEUROD1, and PDX-1 (Keller et al, 2007).
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In molecular biology miR-375 microRNA is a short RNA molecule. MicroRNAs (miRNAs) are small (18-25 nucleotides), non-coding RNAs that regulate genes post-transcriptionally by inhibiting translation and/or causing mRNA degradation. miR-375 is found on human chromosome 2 in between the CRYBA2 and CCDC108 genes.[1]
miR-375 is specifically expressed in the pancreatic islets and brain.[2] miR-375 was one of the first miRNAs identified in the pancreas (Poy et al, 2004), and remains one of the best characterised in terms of function. It is expressed in the pancreas and pituitary gland, organs linked by their role in hormone secretion, and expression levels increase during pancreas organogenesis. Loss-of-function studies showed that miR-375 is essential for β-cell formation in zebrafish (Kloosterman et al, 2007). miR-375 knockout mice have decreased numbers of β-cells and increased numbers of α-cells. The increase in glucagon levels, combined with the reduction in insulin levels, results in hyperglycaemia. This shows the importance of miR-375 in the establishment of normal pancreatic cell mass through the targeting of a group of genes which control cellular growth and proliferation in the developing pancreas (Poy et al, 2009). Further evidence for the involvement of miR-375 in pancreas development includes the fact that its expression is regulated by several transcription factors important in pancreatic development and function, including HNF6, INSM1, NGN3, NEUROD1, and PDX-1 (Keller et al, 2007).
[edit] Role in cancer
miR-375 has been implicated in a number of different cancers including breast and gastric cancer.[3][4][5]
[edit] Targets
microRNAs generally lower the expression of gene targets through interaction with their 3' UTR. miR-375 has been shown to target the MTPN gene, which encodes the myotrophin protein, that regulates hormone release and exocytosis.[6] miR-375 also lowers the level of the PDK-1 gene.[7]
[edit] See also
[edit] References
- ^ Baroukh NN, Van Obberghen E (2009). "Function of microRNA-375 and microRNA-124a in pancreas and brain.". FEBS J 276 (22): 6509–21. doi:10.1111/j.1742-4658.2009.07353.x. PMID 20102393.
- ^ Avnit-Sagi T, Kantorovich L, Kredo-Russo S, Hornstein E, Walker MD (2009). "The promoter of the pri-miR-375 gene directs expression selectively to the endocrine pancreas.". PLoS ONE 4 (4): e5033. doi:10.1371/journal.pone.0005033. PMC 2660411. PMID 19343226. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2660411/.
- ^ de Souza Rocha Simonini P, Breiling A, Gupta N, Malekpour M, Youns M, Omranipour R, Malekpour F, Volinia S, Croce CM, Najmabadi H, Diederichs S, Sahin O, Mayer D, Lyko F, Hoheisel JD, Riazalhosseini Y (2010). "Epigenetically Deregulated microRNA-375 Is Involved in a Positive Feedback Loop with Estrogen Receptor {alpha} in Breast Cancer Cells.". Cancer Res 70 (22): 9175–84. doi:10.1158/0008-5472.CAN-10-1318. PMID 20978187.
- ^ Ding L, Xu Y, Zhang W, Deng Y, Si M, Du Y, Yao H, Liu X, Ke Y, Si J, Zhou T (2010). "MiR-375 frequently downregulated in gastric cancer inhibits cell proliferation by targeting JAK2.". Cell Res 20 (7): 784–93. doi:10.1038/cr.2010.79. PMID 20548334.
- ^ Tsukamoto Y, Nakada C, Noguchi T, Tanigawa M, Nguyen LT, Uchida T, Hijiya N, Matsuura K, Fujioka T, Seto M, Moriyama M (2010). "MicroRNA-375 is downregulated in gastric carcinomas and regulates cell survival by targeting PDK1 and 14-3-3zeta.". Cancer Res 70 (6): 2339–49. doi:10.1158/0008-5472.CAN-09-2777. PMID 20215506.
- ^ Li Y, Xu X, Liang Y, Liu S, Xiao H, Li F, Cheng H, Fu Z (2010). "miR-375 enhances palmitate-induced lipoapoptosis in insulin-secreting NIT-1 cells by repressing myotrophin (V1) protein expression.". Int J Clin Exp Pathol 3 (3): 254–64. PMC 2836503. PMID 20224724. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2836503/.
- ^ El Ouaamari A, Baroukh N, Martens GA, Lebrun P, Pipeleers D, van Obberghen E (2008). "miR-375 targets 3'-phosphoinositide-dependent protein kinase-1 and regulates glucose-induced biological responses in pancreatic beta-cells.". Diabetes 57 (10): 2708–17. doi:10.2337/db07-1614. PMID 18591395.
[edit] Further reading
- ^ Abdelmohsen K, Hutchison ER, Lee EK, Kuwano Y, Kim MM, Masuda K, Srikantan S, Subaran SS, Marasa BS, Mattson MP, Gorospe M (2010). "miR-375 inhibits differentiation of neurites by lowering HuD levels.". Mol Cell Biol 30 (17): 4197–210. doi:10.1128/MCB.00316-10. PMID 20584986.
- ^ Zhao H, Guan J, Lee HM, Sui Y, He L, Siu JJ, Tse PP, Tong PC, Lai FM, Chan JC (2010). "Up-regulated pancreatic tissue microRNA-375 associates with human type 2 diabetes through beta-cell deficit and islet amyloid deposition.". Pancreas 39 (6): 843–6. doi:10.1097/MPA.0b013e3181d12613. PMID 20467341.
- ^ Liu AM, Poon RT, Luk JM (2010). "MicroRNA-375 targets Hippo-signaling effector YAP in liver cancer and inhibits tumor properties.". Biochem Biophys Res Commun 394 (3): 623–7. doi:10.1016/j.bbrc.2010.03.036. PMID 20226166.
- ^ Poy MN, Hausser J, Trajkovski M, Braun M, Collins S, Rorsman P, Zavolan M, Stoffel M (2009). "miR-375 maintains normal pancreatic alpha- and beta-cell mass.". Proc Natl Acad Sci U S A 106 (14): 5813–8. doi:10.1073/pnas.0810550106. PMID 19289822.
- ^ Kloosterman WP, Lagendijk AK, Ketting RF, Moulton JD, Plasterk RH (2007). "Targeted inhibition of miRNA maturation with morpholinos reveals a role for miR-375 in pancreatic islet development.". PLoS Biol 5 (8): e203. doi:10.1371/journal.pbio.0050203. PMC 1925136. PMID 17676975. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1925136/.
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