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Biochem Biophys Res Commun. 2018 Mar 4;497(2):667-674. doi: 10.1016/j.bbrc.2018.02.129. Epub 2018 Feb 17.

MiR-29 family members interact with SPARC to regulate glucose metabolism.

Author information

1
Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Harbin Medical University, Hormone and Endocrinology Key Laboratory of Harbin Medical University, Xuefu Road 246, Harbin, 150080, China.
2
Department of Basic Medical Sciences, Jiangnan University Wuxi College of Medicine, Wuxi, Jiangsu, 214122, China.
3
Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Harbin Medical University, Hormone and Endocrinology Key Laboratory of Harbin Medical University, Xuefu Road 246, Harbin, 150080, China. Electronic address: wwei19742007@hotmail.com.

Abstract

MicroRNA (miR)-29 family members have been reported to play important regulatory roles in metabolic disease. We used TargetScan to show that "secreted protein acidic rich in cysteine" (SPARC) is a target of the miR-29s. SPARC is a multifunctional secretory protein involved in a variety of biological activities, and SPARC dysregulation is associated with a wide range of obesity-related disorders, including type 2 diabetes mellitus (T2DM). We explored whether miR-29s played roles in glucose metabolism and whether miR-29s directly targeted SPARC. We also examined the effect of SPARC on glucose metabolism and how the association of miR-29s with SPARC affected glucose metabolism. We found that overexpression of miR-29s reduced glucose uptake and GLUT4 levels; that miR-29 directly targeted SPARC, resulting in degradation of SPARC-encoding mRNA and reduction in the SPARC protein level; that SPARC increased glucose uptake and GLUT4 levels; that shRNA-mediated knockdown of SPARC reduced GLUT4 protein levels in 3T3-L1 adipocytes; that miR-29s reduced glucose uptake and GLUT4 levels; and that miR-29s inhibited glucose uptake by suppressing SPARC synthesis. Thus, the miR-29 family negatively regulates glucose metabolism by inhibiting SPARC expression.

KEYWORDS:

GLUT4; Glucose metabolism; Glucose uptake; MiR-29 family members; Secreted protein acidic rich in cysteine

PMID:
29462611
DOI:
10.1016/j.bbrc.2018.02.129
[Indexed for MEDLINE]

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