MiR-27 explained

miR-27
Symbol:miR-27
Rfam:RF00644
Mirbase:MI0000085
Mirbase Family:MIPF0000036
Rna Type:miRNA
Tax Domain:Animalia
Entrezgene:407018
Hgncid:31613
Chromosome:19

miR-27 is a family of microRNA precursors found in animals, including humans.[1] MicroRNAs are typically transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~22 nucleotide product.[2] The excised region or, mature product, of the miR-27 precursor is the microRNA mir-27.

Herpesvirus saimiri expresses several non-coding RNAs (HSURs) which have been found to significantly reduce the level of mir-27 in a host cell.[3] It has been proposed that miR-27 operates together with miR-23 and mir-24 in a co-operative cluster.[4]

Regulation of adipocyte differentiation

miR-27 is one of a number of microRNAs implicated in cholesterol homeostasis and fatty acid metabolism.[5] The miR-27 gene family has been shown to be downregulated during the differentiation of adipocytes. miR-27 inhibits adipocyte formation when overexpressed, acting by blocking the expression of two main regulators of adipogenesis.[6] MicroRNAs miR-27a and -27b have been found to negatively regulate adipocyte differentiation through regulation of the peroxisome proliferator-activated receptor gamma (PPARγ) post-transcriptionally, as well as C/EBP alpha in the case of miR-27b.[7] miR-27 can be identified both as an adipogenic inhibitor and as playing an important role in the development of obesity.[6]

Wnt signalling pathway

miR-27 is an activator of the Wnt signalling pathway, affecting the differentiation of mesenchymal stem cells into osteoblasts.[8] miR-27 has been found to target and inhibit gene expression of the adenomatous polyposis coli (APC) protein, enabling it to regulate osteoblast differentiation. Expression levels of miR-27 are positively correlated with beta-catenin,[9] a key protein in Wnt signalling. There is activation of Wnt signalling through nuclear accumulation of this protein, which is in response to inhibition of the beta-catenin destruction complex. This in turn is brought about by APC inhibition of miR-27.[9]

Cancer Regulation

miR-27 is known to regulate components involved in numerous types of cancer, including breast[10] [11] and ovarian.[12] miR-27a has been identified as an oncogenic microRNA and, specifically, is highly expressed in breast cancer cells. mir-27b expression is associated with survival in triple negative breast cancer patients.[13] Inhibition of miR-27 by antisense molecules decreases cell proliferation.[14] Antisense RNA directed against miR-27a has been shown to decrease the percentage of cells in S phase whilst also increasing those in the G2-M phase.[15]

The FOXO (Forkhead Box O) gene sub-family encodes tumour-suppressive transcription factors that regulate multiple aspects of cell cycle progression and survival. FOXO1 protein expression is down-regulated in breast tumour tissue samples; miR-27a has been identified as one of three miRNAS (along with miR-96 and miR-182) which directly target FOXO1 and regulate its endogenous expression. Suppression of miR-27a results in a FOXO1 protein increase and a consequent cell number decrease.[15]

Notes and References

  1. Landgraf. P. Rusu, M . Sheridan, R . Sewer, A . Iovino, N . Aravin, A . Pfeffer, S . Rice, A. A mammalian microRNA expression atlas based on small RNA library sequencing.. Cell. Jun 29, 2007. 129. 7. 1401–14. 17604727. 10.1016/j.cell.2007.04.040. 2681231. etal.
  2. Ambros . V . 2001 . microRNAs: tiny regulators with great potential . Cell . 107 . 823 - 826 . 11779458 . 10.1016/S0092-8674(01)00616-X . 7. 14574186 . free .
  3. Cazalla. D. Yario, T . Steitz, JA . Down-regulation of a host microRNA by a Herpesvirus saimiri noncoding RNA.. Science. Jun 18, 2010. 328. 5985. 1563–6. 20558719. 10.1126/science.1187197. 3075239. 2010Sci...328.1563C.
  4. Chhabra. R. Dubey, R . Saini, N . Cooperative and individualistic functions of the microRNAs in the miR-23a~27a~24-2 cluster and its implication in human diseases.. Molecular Cancer. Sep 3, 2010. 9. 232. 20815877. 10.1186/1476-4598-9-232. 2940846. free.
  5. Fernández-Hernando. C. Suárez, Y . Rayner, KJ . Moore, KJ . MicroRNAs in lipid metabolism.. Current Opinion in Lipidology. April 2011. 22. 2. 86–92. 21178770. 10.1097/MOL.0b013e3283428d9d. 3096067.
  6. Lin Q, Gao Z, Alarcon RM, Ye J, Yun Z . A role of miR-27 in the regulation of adipogenesis. . FEBS J . 2009 . 276 . 8 . 2348–58 . 19348006 . 10.1111/j.1742-4658.2009.06967.x. 5330386.
  7. Kim SY, Kim AY, Lee HW, Son YH, Lee GY, Lee JW, etal . miR-27a is a negative regulator of adipocyte differentiation via suppressing PPARgamma expression. . Biochem Biophys Res Commun . 2010 . 392 . 3 . 323–8 . 20060380 . 10.1016/j.bbrc.2010.01.012 .
  8. Wang. T. Xu, Z. miR-27 promotes osteoblast differentiation by modulating Wnt signaling.. Biochemical and Biophysical Research Communications. Nov 12, 2010. 402. 2. 186–9. 20708603. 10.1016/j.bbrc.2010.08.031.
  9. Wang T, Xu Z . miR-27 promotes osteoblast differentiation by modulating Wnt signaling. . Biochem Biophys Res Commun . 2010 . 402 . 2 . 186–9 . 20708603 . 10.1016/j.bbrc.2010.08.031 .
  10. Li. X . Mertens-Talcott, SU . Zhang, S . Kim, K . Ball, J . Safe, S. MicroRNA-27a Indirectly Regulates Estrogen Receptor Expression and Hormone Responsiveness in MCF-7 Breast Cancer Cells.. Endocrinology. June 2010. 151. 6. 2462–73. 20382698. 10.1210/en.2009-1150. 2875816.
  11. Guttilla. IK. White, BA. Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells.. The Journal of Biological Chemistry. Aug 28, 2009. 284. 35. 23204–16. 19574223. 10.1074/jbc.M109.031427. 2749094. free .
  12. Kontorovich. T. Levy, A . Korostishevsky, M . Nir, U . Friedman, E . Single nucleotide polymorphisms in miRNA binding sites and miRNA genes as breast/ovarian cancer risk modifiers in Jewish high-risk women.. International Journal of Cancer. Aug 1, 2010. 127. 3. 589–97. 19950226. 10.1002/ijc.25065. 29984487.
  13. Lánczky. András. Nagy. Ádám. Bottai. Giulia. Munkácsy. Gyöngyi. Szabó. András. Santarpia. Libero. Győrffy. Balázs. 2016-12-01. 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. 10.1007/s10549-016-4013-7. 1573-7217. 27744485. 11165696.
  14. Mertens-Talcott SU, Chintharlapalli S, Li X, Safe S . The oncogenic microRNA-27a targets genes that regulate specificity protein transcription factors and the G2-M checkpoint in MDA-MB-231 breast cancer cells. . Cancer Res . 2007 . 67 . 22 . 11001–11 . 18006846 . 10.1158/0008-5472.CAN-07-2416 . free .
  15. Guttilla IK, White BA . Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells. . J Biol Chem . 2009 . 284 . 35 . 23204–16 . 19574223 . 10.1074/jbc.M109.031427 . 2749094 . free .

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