Mir-126 Suppresses The Glucose-Stimulated Proliferation Via Irs-2 In Ins-1 Beta Cells
PLOS ONE(2016)
Abstract
BackgroundIncreasing evidence suggests that miR-126 participates in the glucose homeostasis through its target molecules. Although bioinformatics analysis predicts that miR-126 can bind with the insulin receptor substrate-2(IRS-2) mRNA at the "seed sequence", but there are still no definitely reports to support it. In this study, we provided evidences that IRS-2 was one of the target genes of miR-126. And miR-126 has a proliferation inhibiting effects in INS-1 beta cells, mainly through the suppression of IRS-2.MethodsThe 3'-UTR of IRS-2 regulated by miR-126 was analyzed by the luciferase assay and western blot. Furthermore, proliferation of INS-1 beta cells stimulated by glucose was tested, and the association between IRS-2 and miR-126 were analyzed.ResultsWe found that mutation of only three of the 6 "seed sequences" can eliminate the inhibition effect of miR-126. In INS-1 beta cells, administration of miR-126 suppresses the proliferation, together with the unbalanced down-regulation of IRS-2 and IRS-1. Over-expression of IRS-2 can reverse the proliferation effect of miR-126, while not of IRS-1. These results suggested that miR-126 inhibited the beta-cell proliferation via the inhibition of IRS-2 instead of IRS-1. Additionally, we also found that high glucose and insulin could stimulate the rapid production of endogenous miR-126 within 6 hours, together with the short term suppression of IRS-1 and IRS-2 expression, and intensify the unbalanced expression of IRS-1 and IRS-2.ConclusionsIRS-2 was one of the targets of miR-126. MiR-126 inhibited the beta-cell proliferation through IRS-2 instead of IRS-1. MiR-126 may take part in the glucose homeostasis both through its target IRS-2 and IRS-1. The unbalance between IRS-1 and IRS-2 caused by miR-126 may play an important role in type 2 diabetes.
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Key words
cells,glucose-stimulated
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