The H19/let-7 double-negative feedback loop contributes to glucose metabolism in muscle cells

Gao, Yuan; Wu, Fuju; Zhou, Jichun; Yan, Lei; Jurczak, Michael J; Lee, Hui-Young; Yang, Lihua; Müller, Martin; Zhou, Xiao-Bo; Dandolo, Luisa; Szendroedi, Julia; Roden, Michael; Flannery, Clare; Taylor, Hugh; Carmichael, Gordon G; Shulman, Gerald I; Huang, Yingqun (2014). The H19/let-7 double-negative feedback loop contributes to glucose metabolism in muscle cells. Nucleic acids research, 42(22), pp. 13799-13811. Oxford University Press 10.1093/nar/gku1160

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The H19 lncRNA has been implicated in development and growth control and is associated with human genetic disorders and cancer. Acting as a molecular sponge, H19 inhibits microRNA (miRNA) let-7. Here we report that H19 is significantly decreased in muscle of human subjects with type-2 diabetes and insulin resistant rodents. This decrease leads to increased bioavailability of let-7, causing diminished expression of let-7 targets, which is recapitulated in vitro where H19 depletion results in impaired insulin signaling and decreased glucose uptake. Furthermore, acute hyperinsulinemia downregulates H19, a phenomenon that occurs through PI3K/AKT-dependent phosphorylation of the miRNA processing factor KSRP, which promotes biogenesis of let-7 and its mediated H19 destabilization. Our results reveal a previously undescribed double-negative feedback loop between sponge lncRNA and target miRNA that contributes to glucose regulation in muscle cells.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Gynaecology

UniBE Contributor:

Müller, Martin

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0305-1048

Publisher:

Oxford University Press

Language:

English

Submitter:

Nathalie Ursula Becher

Date Deposited:

13 May 2015 11:22

Last Modified:

28 Apr 2018 02:31

Publisher DOI:

10.1093/nar/gku1160

PubMed ID:

25399420

BORIS DOI:

10.7892/boris.68917

URI:

https://boris.unibe.ch/id/eprint/68917

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