Mir-375

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mir-375
RF00700.png
Conserved secondary structure of mir-375
Identifiers
Symbol mir-375
Rfam RF00700
miRBase family MIPF0000114
Other data
RNA type microRNA
Domain(s) Eukaryota;
SO {{{SO}}}

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, brain and spinal cord.[2][3] 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).

Role in cancer[edit]

miR-375 has been implicated in a number of different cancers including breast and gastric cancer.[4][5][6] It has been used in miR fluorescence in situ hybridization to distinguish Merkel cell polyomavirus-positive Merkel cell carcinoma from other common skin cancers.[7]

Targets[edit]

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.[8] miR-375 also lowers the level of the PDK-1 gene.[9]

See also[edit]

References[edit]

  1. ^ 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. 
  2. ^ 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 2660411Freely accessible. PMID 19343226. 
  3. ^ Bhinge A, Namboori SC, Bithell A, Soldati C, Buckley NJ, Stanton LW (2016). "MiR-375 is Essential for Human Spinal Motor Neuron Development and May Be Involved in Motor Neuron Degeneration.". Stem Cells. 34 (1): 124–134. doi:10.1002/stem.2233. PMID 26507573. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ Renwick N, Cekan P, Masry PA, McGeary SE, Miller JB, Hafner M, Li Z, Mihailovic A, Morozov P, Brown M, Gogakos T, Mobin MB, Snorrason EL, Feilotter HE, Zhang X, Perlis CS, Wu H, Suárez-Fariñas M, Feng H, Shuda M, Moore PS, Tron VA, Chang Y, Tuschl T (2013). "Multicolor microRNA FISH effectively differentiates tumor types.". J Clin Invest. 123 (6): 2694–702. doi:10.1172/JCI68760. PMID 23728175. 
  8. ^ 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 2836503Freely accessible. PMID 20224724. 
  9. ^ 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. PMC 2551681Freely accessible. PMID 18591395. 

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