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==Regulation of adipocyte differentiation==
==Regulation of adipocyte differentiation==
miR-27 is one of a number of microRNAs implicated in [[cholesterol]] homeostasis and [[fatty acid metabolism]].<ref>{{cite journal|last=Fernández-Hernando|first=C|author2=Suárez, Y |author3=Rayner, KJ |author4=Moore, KJ |title=MicroRNAs in lipid metabolism.|journal=Current Opinion in Lipidology|date=April 2011|volume=22|issue=2|pages=86–92|pmid=21178770|doi=10.1097/MOL.0b013e3283428d9d|pmc=3096067}}</ref> 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]].<ref name="pmid19348006">{{cite journal|vauthors=Lin Q, Gao Z, Alarcon RM, Ye J, Yun Z | title=A role of miR-27 in the regulation of adipogenesis. | journal=FEBS J | year= 2009 | volume= 276 | issue= 8 | pages= 2348–58 | pmid=19348006 | doi= 10.1111/j.1742-4658.2009.06967.x| pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19348006  }}</ref> MicroRNAs miR-27a and -27b have been found to negatively regulate adipocyte differentiation through regulation of the [[peroxisome proliferator-activated receptor gamma|peroxisome proliferator-activated receptor gamma (PPARγ)]] post-transcriptionally, as well as [[CEBPA|C/EBP alpha]] in the case of miR-27b.<ref name="pmid20060380">{{cite journal |vauthors=Kim SY, Kim AY, Lee HW, Son YH, Lee GY, Lee JW, etal | title=miR-27a is a negative regulator of adipocyte differentiation via suppressing PPARgamma expression. | journal=Biochem Biophys Res Commun | year= 2010 | volume= 392 | issue= 3 | pages= 323–8 | pmid=20060380 | doi=10.1016/j.bbrc.2010.01.012 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20060380  }}</ref>  miR-27 can be identified both as an adipogenic inhibitor and as playing an important role in the development of obesity.<ref name="pmid19348006"/>
miR-27 is one of a number of microRNAs implicated in [[cholesterol]] homeostasis and [[fatty acid metabolism]].<ref>{{cite journal|last=Fernández-Hernando|first=C|author2=Suárez, Y |author3=Rayner, KJ |author4=Moore, KJ |title=MicroRNAs in lipid metabolism.|journal=Current Opinion in Lipidology|date=April 2011|volume=22|issue=2|pages=86–92|pmid=21178770|doi=10.1097/MOL.0b013e3283428d9d|pmc=3096067}}</ref> 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]].<ref name="pmid19348006">{{cite journal|vauthors=Lin Q, Gao Z, Alarcon RM, Ye J, Yun Z | title=A role of miR-27 in the regulation of adipogenesis. | journal=FEBS J | year= 2009 | volume= 276 | issue= 8 | pages= 2348–58 | pmid=19348006 | doi= 10.1111/j.1742-4658.2009.06967.x| pmc= 5330386| url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19348006  }}</ref> MicroRNAs miR-27a and -27b have been found to negatively regulate adipocyte differentiation through regulation of the [[peroxisome proliferator-activated receptor gamma|peroxisome proliferator-activated receptor gamma (PPARγ)]] post-transcriptionally, as well as [[CEBPA|C/EBP alpha]] in the case of miR-27b.<ref name="pmid20060380">{{cite journal |vauthors=Kim SY, Kim AY, Lee HW, Son YH, Lee GY, Lee JW, etal | title=miR-27a is a negative regulator of adipocyte differentiation via suppressing PPARgamma expression. | journal=Biochem Biophys Res Commun | year= 2010 | volume= 392 | issue= 3 | pages= 323–8 | pmid=20060380 | doi=10.1016/j.bbrc.2010.01.012 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20060380  }}</ref>  miR-27 can be identified both as an adipogenic inhibitor and as playing an important role in the development of obesity.<ref name="pmid19348006"/>


==Wnt signalling pathway==
==Wnt signalling pathway==
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==Cancer Regulation==
==Cancer Regulation==
miR-27 is known to regulate components involved in numerous types of cancer, including [[breast cancer|breast]]<ref>{{cite journal|last=Li|first=X |author2=Mertens-Talcott, SU |author3=Zhang, S |author4=Kim, K |author5=Ball, J |author6=Safe, S|title=MicroRNA-27a Indirectly Regulates Estrogen Receptor {alpha} Expression and Hormone Responsiveness in MCF-7 Breast Cancer Cells.|journal=Endocrinology|date=June 2010|volume=151|issue=6|pages=2462–73|pmid=20382698|doi=10.1210/en.2009-1150|pmc=2875816}}</ref><ref>{{cite journal|last=Guttilla|first=IK|author2=White, BA|title=Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells.|journal=The Journal of Biological Chemistry|date=Aug 28, 2009|volume=284|issue=35|pages=23204–16|pmid=19574223|doi=10.1074/jbc.M109.031427|pmc=2749094}}</ref> and [[ovarian cancer|ovarian]].<ref>{{cite journal|last=Kontorovich|first=T|author2=Levy, A |author3=Korostishevsky, M |author4=Nir, U |author5=Friedman, E |title=Single nucleotide polymorphisms in miRNA binding sites and miRNA genes as breast/ovarian cancer risk modifiers in Jewish high-risk women.|journal=International Journal of Cancer|date=Aug 1, 2010|volume=127|issue=3|pages=589–97|pmid=19950226|doi=10.1002/ijc.25065}}</ref> 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.<ref>{{Cite journal|last=Lánczky|first=András|last2=Nagy|first2=Ádám|last3=Bottai|first3=Giulia|last4=Munkácsy|first4=Gyöngyi|last5=Szabó|first5=András|last6=Santarpia|first6=Libero|last7=Győrffy|first7=Balázs|date=2016-12-01|title=miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients|url=https://www.ncbi.nlm.nih.gov/pubmed/27744485|journal=Breast Cancer Research and Treatment|volume=160|issue=3|pages=439–446|doi=10.1007/s10549-016-4013-7|issn=1573-7217|pmid=27744485}}</ref> Inhibition of miR-27 by antisense molecules decreases cell proliferation.<ref name="pmid18006846">{{cite journal|vauthors=Mertens-Talcott SU, Chintharlapalli S, Li X, Safe S | title=The oncogenic microRNA-27a targets genes that regulate specificity protein transcription factors and the G2-M checkpoint in MDA-MB-231 breast cancer cells. | journal=Cancer Res | year= 2007 | volume= 67 | issue= 22 | pages= 11001–11 | pmid=18006846 | doi=10.1158/0008-5472.CAN-07-2416 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18006846  }}</ref> 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.<ref name="pmid19574223">{{cite journal|vauthors=Guttilla IK, White BA | title=Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells. | journal=J Biol Chem | year= 2009 | volume= 284 | issue= 35 | pages= 23204–16 | pmid=19574223 | doi=10.1074/jbc.M109.031427 | pmc=2749094 }}</ref>
miR-27 is known to regulate components involved in numerous types of cancer, including [[breast cancer|breast]]<ref>{{cite journal|last=Li|first=X |author2=Mertens-Talcott, SU |author3=Zhang, S |author4=Kim, K |author5=Ball, J |author6=Safe, S|title=MicroRNA-27a Indirectly Regulates Estrogen Receptor {alpha} Expression and Hormone Responsiveness in MCF-7 Breast Cancer Cells.|journal=Endocrinology|date=June 2010|volume=151|issue=6|pages=2462–73|pmid=20382698|doi=10.1210/en.2009-1150|pmc=2875816}}</ref><ref>{{cite journal|last=Guttilla|first=IK|author2=White, BA|title=Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells.|journal=The Journal of Biological Chemistry|date=Aug 28, 2009|volume=284|issue=35|pages=23204–16|pmid=19574223|doi=10.1074/jbc.M109.031427|pmc=2749094}}</ref> and [[ovarian cancer|ovarian]].<ref>{{cite journal|last=Kontorovich|first=T|author2=Levy, A |author3=Korostishevsky, M |author4=Nir, U |author5=Friedman, E |title=Single nucleotide polymorphisms in miRNA binding sites and miRNA genes as breast/ovarian cancer risk modifiers in Jewish high-risk women.|journal=International Journal of Cancer|date=Aug 1, 2010|volume=127|issue=3|pages=589–97|pmid=19950226|doi=10.1002/ijc.25065}}</ref> 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.<ref>{{Cite journal|last=Lánczky|first=András|last2=Nagy|first2=Ádám|last3=Bottai|first3=Giulia|last4=Munkácsy|first4=Gyöngyi|last5=Szabó|first5=András|last6=Santarpia|first6=Libero|last7=Győrffy|first7=Balázs|date=2016-12-01|title=miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients|journal=Breast Cancer Research and Treatment|volume=160|issue=3|pages=439–446|doi=10.1007/s10549-016-4013-7|issn=1573-7217|pmid=27744485}}</ref> Inhibition of miR-27 by antisense molecules decreases cell proliferation.<ref name="pmid18006846">{{cite journal|vauthors=Mertens-Talcott SU, Chintharlapalli S, Li X, Safe S | title=The oncogenic microRNA-27a targets genes that regulate specificity protein transcription factors and the G2-M checkpoint in MDA-MB-231 breast cancer cells. | journal=Cancer Res | year= 2007 | volume= 67 | issue= 22 | pages= 11001–11 | pmid=18006846 | doi=10.1158/0008-5472.CAN-07-2416 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18006846  }}</ref> 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.<ref name="pmid19574223">{{cite journal|vauthors=Guttilla IK, White BA | title=Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells. | journal=J Biol Chem | year= 2009 | volume= 284 | issue= 35 | pages= 23204–16 | pmid=19574223 | doi=10.1074/jbc.M109.031427 | pmc=2749094 }}</ref>


The [[FOXO|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.<ref name="pmid19574223"/>
The [[FOXO|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.<ref name="pmid19574223"/>

Latest revision as of 15:21, 18 May 2018

miR-27
File:Mir-27 SS.png
Conserved secondary structure of miR-27 prescursor
Identifiers
SymbolmiR-27
RfamRF00644
miRBaseMI0000085
miRBase familyMIPF0000036
Entrez407018
HUGO31613
Other data
RNA typemiRNA
Domain(s)Animalia
LocusChr. 19 [1]
PDB structuresPDBe

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]

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&ndash, 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. ↑ 6.0 6.1 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. ↑ 9.0 9.1 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. ↑ 15.0 15.1 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.

External links

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