miR-27

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miR-27
Mir-27 SS.png
Conserved secondary structure of miR-27 prescursor
Identifiers
Symbol miR-27
Rfam RF00644
miRBase MI0000085
miRBase family MIPF0000036
Entrez 407018
HUGO 31613
Other data
RNA type miRNA
Domain(s) Animalia
Locus Chr. 19 [1]

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[edit]

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 overexpression 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[edit]

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[edit]

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. Inhibition of miR-27 by antisense molecules decreases cell proliferation.[13] 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.[14]

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.[14]

References[edit]

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

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