MiRNA-221 protects islet β cell function in gestational diabetes mellitus by targeting PAK1

To elucidate the potential function of miRNA-221 in gestational diabetes mellitus (GDM) and the underlying mechanism. MiRNA-221 level was analyzed in the microarray containing placental tissues of GDM rats. After constructing GDM model in rats, miRNA-221 level in placental tissues of GDM rats or controls was determined as well. The relationship between miRNA-221 level and blood glucose in GDM rats was analyzed by Spearman correlation test. Regulatory effects of miRNA-221 on proliferation, apoptosis and insulin secretion in INS-1 cells were assessed. Through dual-luciferase reporter gene assay, the direct target of miRNA-221, PAK1 was identified. At last, potential influences of miRNA-221/PAK1 axis on INS-1 cell phenotypes were determined. MiRNA-221 was downregulated in placental tissues of GDM rats, and its level was negatively correlated to that of blood glucose level in GDM rats. Overexpression of miRNA-221 stimulated insulin secretion, cell proliferation and suppressed apoptosis in INS-1 cells. Knockdown of miRNA-221 achieved the opposite results. PAK1 was proved as the direct target of miRNA-221. Notably, PAK1 was able to reverse regulatory effects of miRNA-221 on INS-1 cell phenotypes. MiRNA-221 regulates proliferation, apoptosis and insulin secretion in islet beta cells through targeting PAK1, thus protecting GDM-induced islet dysfunction. (C) 2019 Elsevier Inc. All rights reserved.