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.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Gao Y,Wu F,Zhou J,Yan L,Jurczak MJ,Lee HY,Yang L,Mueller M,Zhou XB,Dandolo L,Szendroedi J,Roden M,Flannery C,Taylor H,Carmichael GG,Shulman GI,Huang Ydoi
10.1093/nar/gku1160subject
Has Abstractpub_date
2014-12-16 00:00:00pages
13799-811issue
22eissn
0305-1048issn
1362-4962pii
gku1160journal_volume
42pub_type
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