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

被引：260

作者：

Gao, Yuan ^{[1
,2
]}

Wu, Fuju ^{[1
,3
]}

Zhou, Jichun ^{[1
,4
]}

Yan, Lei ^{[1
,5
]}

Jurczak, Michael J. ^{[6
,7
,8
,9
]}

Lee, Hui-Young ^{[6
,7
,8
,9
]}

Yang, Lihua ^{[1
,10
]}

Mueller, Martin ^{[1
,11
]}

Zhou, Xiao-Bo ^{[1
,12
]}

Dandolo, Luisa ^{[13
]}

Szendroedi, Julia ^{[14
,15
]}

Roden, Michael ^{[14
,15
]}

Flannery, Clare ^{[1
]}

Taylor, Hugh ^{[1
]}

Carmichael, Gordon G. ^{[16
]}

Shulman, Gerald I. ^{[6
,7
,8
,9
]}

Huang, Yingqun ^{[1
]}

机构：

[1] Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, Yale Stem Cell Ctr, New Haven, CT 06510 USA

[2] Chinese Peoples Liberat Army Gen Hosp, Dept Gynecol & Obstet, Beijing 100853, Peoples R China

[3] Jilin Univ, Dept Obstet & Gynecol, Changchun 130021, Jilin, Peoples R China

[4] Zhejiang Univ, Sch Med, Dept Surg Oncol, Affiliated Sir Run Run Shaw Hosp, Hangzhou 310016, Zhejiang, Peoples R China

[5] Shandong Univ, Dept Obstet & Gynecol, Shandong Prov Hosp, Jinan 250021, Shandong, Peoples R China

[6] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA

[7] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA

[8] Yale Univ, Sch Med, Dept Cellular Physiol, New Haven, CT 06510 USA

[9] Yale Univ, Sch Med, Dept Mol Physiol, New Haven, CT 06510 USA

[10] Tangshan Gongren Hosp, Dept Obstet & Gynecol, Tangshan 063000, Hebei, Peoples R China

[11] Univ Hosp Bern, Dept Obstet & Gynecol, CH-3012 Bern, Switzerland

[12] Xi An Jiao Tong Univ, Dept Immunol & Pathogen Biol, Sch Med, Xian 710061, Shaanxi, Peoples R China

[13] Inst Cochin Genet Mol, Dept Genet & Dev, U1016, F-75014 Paris, France

[14] Leibniz Ctr Diabet Res, Inst Clin Diabetol, German Diabet Ctr, D-40225 Dusseldorf, Germany

[15] Univ Dusseldorf, Dept Metab Dis, D-40225 Dusseldorf, Germany

[16] Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Farmington, CT 06030 USA

来源：

NUCLEIC ACIDS RESEARCH | 2014年 / 42卷 / 22期

关键词：

LONG NONCODING RNA; LIPOPROTEIN-LIPASE; CANCER METASTASIS; H19; KSRP; MICRORNA; GROWTH; PROTEIN; LIN28; GENE;

D O I：

10.1093/nar/gku1160

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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 down-regulates 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.

引用

页码：13799 / 13811

页数：13

共 45 条

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