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

ABSTRACT: 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.

SUBMITTER: Gao Y

PROVIDER: S-EPMC4267628 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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

Gao Yuan Y Wu Fuju F Zhou Jichun J Yan Lei L Jurczak Michael J MJ Lee Hui-Young HY Yang Lihua L Mueller Martin M Zhou Xiao-Bo XB Dandolo Luisa L Szendroedi Julia J Roden Michael M Flannery Clare C Taylor Hugh H Carmichael Gordon G GG Shulman Gerald I GI Huang Yingqun Y

Nucleic acids research 20141115 22

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 impa ...[more]

PMID: 25399420

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

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

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