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PLoS One. 2015 Feb 6;10(2):e0116067. doi: 10.1371/journal.pone.0116067. eCollection 2015.

MicroRNA-185 targets SOCS3 to inhibit beta-cell dysfunction in diabetes.

Author information

1
Department of Pharmacy, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China.
2
Department of Endocrinology, Liaocheng People's Hospital, Shandong, China.
3
Department of General Surgery, Liaocheng People's Hospital, Shandong, China.
4
Research Department, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China.

Abstract

Diabetes is the most common and complex metabolic disorder, and one of the most important health threats now. MicroRNAs (miRNAs) are a group of small non-coding RNAs that have been suggested to play a vital role in a variety of physiological processes, including glucose homeostasis. In this study, we investigated the role of miR-185 in diabetes. MiR-185 was significantly downregulated in diabetic patients and mice, and the low level was correlated to blood glucose concentration. Overexpression of miR-185 enhanced insulin secretion of pancreatic β-cells, promoted cell proliferation and protected cells from apoptosis. Further experiments using in silico prediction, luciferase reporter assay and western blot assay demonstrated that miR-185 directly targeted SOCS3 by binding to its 3'-UTR. On the contrary to miR-185's protective effects, SOCS3 significantly suppressed functions of β-cell and inactivated Stat3 pathway. When treating cells with miR-185 mimics in combination with SOCS3 overexpression plasmid, the inhibitory effects of SOCS3 were reversed. While combined treatment of miR-185 mimics and SOCS3 siRNA induced synergistically promotive effects compared to either miR-185 mimics or SOCS3 siRNA treatment alone. Moreover, we observed that miR-185 level was inversely correlated with SOCS3 expression in diabetes patients. In conclusion, this study revealed a functional and mechanistic link between miR-185 and SOCS3 in the pathogenesis of diabetes. MiR-185 plays an important role in the regulation of insulin secretion and β-cell growth in diabetes. Restoration of miR-185 expression may serve a potentially promising and efficient therapeutic approach for diabetes.

PMID:
25658748
PMCID:
PMC4319748
DOI:
10.1371/journal.pone.0116067
[Indexed for MEDLINE]
Free PMC Article

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