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 (A) |
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: |
29 Mar 2023 23:34 |
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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