Symbol mir-375 miRBase family MIPF0000114 Domain(s) Eukaryota; | Rfam RF00700 RNA type microRNA SO {{{SO}}} | |
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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.
Contents
miR-375 is specifically expressed in the pancreatic islets, brain and spinal cord. 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
miR-375 has been implicated in a number of different cancers including breast and gastric cancer. It has been used in miR fluorescence in situ hybridization to distinguish Merkel cell polyomavirus-positive Merkel cell carcinoma from other common skin cancers.
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. miR-375 also lowers the level of the PDK-1 gene.