Document Detail


MIR-200 is induced by thioredoxin-interacting protein and regulates ZEB1 signaling and beta cell apoptosis.
MedLine Citation:
PMID:  25391656     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Small non-coding microRNAs have emerged as important regulators of cellular processes, but their role in pancreatic beta cells has only started to be elucidated. Loss of pancreatic beta cells is a key factor in the pathogenesis of diabetes and we have demonstrated that beta cell expression of thioredoxin-interacting protein (TXNIP) is increased in diabetes and causes beta cell apoptosis, whereas TXNIP deficiency is protective against diabetes. Recently, we found that TXNIP also impairs beta cell function by inducing microRNA-204. Interestingly, using INS-1 beta cells as well as primary islets we now discovered that expression of another microRNA, miR-200, was induced by TXNIP and by diabetes. Furthermore, we found that miR-200 targeted and decreased Zinc Finger E-Box Binding Homeobox 1 (Zeb1) and promoted beta cell apoptosis as measured by cleaved caspase-3 levels, Bax/Bcl2 ratio, and TUNEL. In addition, Zeb1 knockdown was able to mimic the miR-200 effects on beta cell apoptosis suggesting that Zeb1 plays an important role in mediating the miR-200 effects. Moreover, miR-200 increased beta cell expression of the epithelial marker E-cadherin consistent with inhibition of epithelial-mesenchymal-transition (EMT), a process thought to be involved in beta cell expansion. Thus, we have identified a novel TXNIP-miR-200-Zeb1-E-cadherin signaling pathway that for the first time ties miR-200 to beta cell apoptosis and diabetes and links beta cell TXNIP to EMT. In addition, the present studies shed new light on the regulation and function of miR-200 in beta cells and demonstrate that TXNIP-induced microRNAs control various processes of beta cell biology.
Authors:
Stephen R Filios; Guanlan Xu; Junqin Chen; Kyunghee Hong; Gu Jing; Anath Shalev
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-12
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  -     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-13     Completed Date:  -     Revised Date:  2014-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014, The American Society for Biochemistry and Molecular Biology.
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