miR-27

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.

miR-27
Conserved secondary structure of miR-27 prescursor
Identifiers
SymbolmiR-27
RfamRF00644
miRBaseMI0000085
miRBase familyMIPF0000036
NCBI Gene407018
HGNC31613
Other data
RNA typemiRNA
Domain(s)Animalia
LocusChr. 19
PDB structuresPDBe

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]

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References
  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. Bibcode:2010Sci...328.1563C. 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. 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. PMC 5330386. 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. 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 (June 2010). "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. 127 (3): 589–97. doi:10.1002/ijc.25065. PMID 19950226.
  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. doi:10.1007/s10549-016-4013-7. ISSN 1573-7217. PMID 27744485.
  14. 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.
  15. 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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