Conserved MicroRNA miR-8/miR-200 and its target USH/FOG2 control growth by regulating PI3K
- PMID: 20005803
- DOI: 10.1016/j.cell.2009.11.020
Conserved MicroRNA miR-8/miR-200 and its target USH/FOG2 control growth by regulating PI3K
Abstract
How body size is determined is a long-standing question in biology, yet its regulatory mechanisms remain largely unknown. Here, we find that a conserved microRNA miR-8 and its target, USH, regulate body size in Drosophila. miR-8 null flies are smaller in size and defective in insulin signaling in fat body that is the fly counterpart of liver and adipose tissue. Fat body-specific expression and clonal analyses reveal that miR-8 activates PI3K, thereby promoting fat cell growth cell-autonomously and enhancing organismal growth non-cell-autonomously. Comparative analyses identify USH and its human homolog, FOG2, as the targets of fly miR-8 and human miR-200, respectively. USH/FOG2 inhibits PI3K activity, suppressing cell growth in both flies and humans. FOG2 directly binds to p85alpha, the regulatory subunit of PI3K, and interferes with the formation of a PI3K complex. Our study identifies two novel regulators of insulin signaling, miR-8/miR-200 and USH/FOG2, and suggests their roles in adolescent growth, aging, and cancer.
Similar articles
-
MicroRNA-200 promotes lung cancer cell growth through FOG2-independent AKT activation.IUBMB Life. 2015 Sep;67(9):720-5. doi: 10.1002/iub.1412. Epub 2015 Aug 27. IUBMB Life. 2015. PMID: 26314828 Free PMC article.
-
miR-200c Accelerates Hepatic Stellate Cell-Induced Liver Fibrosis via Targeting the FOG2/PI3K Pathway.Biomed Res Int. 2017;2017:2670658. doi: 10.1155/2017/2670658. Epub 2017 Jun 13. Biomed Res Int. 2017. PMID: 28691020 Free PMC article.
-
MicroRNA miR-8 regulates multiple growth factor hormones produced from Drosophila fat cells.Insect Mol Biol. 2015 Jun;24(3):311-8. doi: 10.1111/imb.12156. Epub 2014 Dec 10. Insect Mol Biol. 2015. PMID: 25492518
-
Up-regulation of miR-200b in biliary atresia patients accelerates proliferation and migration of hepatic stallate cells by activating PI3K/Akt signaling.Cell Signal. 2014 May;26(5):925-32. doi: 10.1016/j.cellsig.2014.01.003. Epub 2014 Jan 8. Cell Signal. 2014. PMID: 24412919
-
Multiple targets of the microRNA miR-8 contribute to immune homeostasis in Drosophila.Dev Comp Immunol. 2014 Aug;45(2):245-51. doi: 10.1016/j.dci.2014.03.015. Epub 2014 Mar 30. Dev Comp Immunol. 2014. PMID: 24694685
Cited by
-
Ursolic acid attenuates diabetic mesangial cell injury through the up-regulation of autophagy via miRNA-21/PTEN/Akt/mTOR suppression.PLoS One. 2015 Feb 17;10(2):e0117400. doi: 10.1371/journal.pone.0117400. eCollection 2015. PLoS One. 2015. PMID: 25689721 Free PMC article.
-
Regulation of Body Size and Growth Control.Genetics. 2020 Oct;216(2):269-313. doi: 10.1534/genetics.120.303095. Genetics. 2020. PMID: 33023929 Free PMC article. Review.
-
The microRNA-200 family acts as an oncogene in colorectal cancer by inhibiting the tumor suppressor RASSF2.Oncol Lett. 2019 Oct;18(4):3994-4007. doi: 10.3892/ol.2019.10753. Epub 2019 Aug 16. Oncol Lett. 2019. PMID: 31565080 Free PMC article.
-
MicroRNA-200 family members differentially regulate morphological plasticity and mode of melanoma cell invasion.PLoS One. 2010 Oct 4;5(10):e13176. doi: 10.1371/journal.pone.0013176. PLoS One. 2010. PMID: 20957176 Free PMC article.
-
Gene regulatory network stabilized by pervasive weak repressions: microRNA functions revealed by the May-Wigner theory.Natl Sci Rev. 2019 Nov;6(6):1176-1188. doi: 10.1093/nsr/nwz076. Epub 2019 Jul 25. Natl Sci Rev. 2019. PMID: 34691996 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases