Abstract
Gestational diabetes mellitus (GDM) is a common metabolic disease during pregnancy with serious harm. However, the pathogenesis of GDM has not been thoroughly studied. Recent reports have shown that microRNAs (miRNAs) are associated with GDM, but the mechanisms remain unclear. This study aimed to investigate the role of miR-142-3p in β cells of GDM. We established GDM mouse models by injecting streptozotocin (STZ) to extract embryonic tissue, peripheral blood and pancreas. qRT-PCR was used to detect the expression of miR-142-3p and FOXO1. 5-ethynyl-2'-deoxyuridine (EDU) staining and flow cytometry were used to measure cell proliferation and apoptosis. Western blot analysis was used to determine the expression of proliferation and apoptosis-related proteins. Dual-luciferase reporter assay was used to assess the target relationship between miR-142-3p and FOXO1. The results showed that miR-142-3p was up-regulated in embryonic tissue and peripheral blood of GDM model mice. Overexpression of miR-142-3p and knockdown of FOXO1 both promoted INS-1 cell proliferation, inhibited apoptosis, increased proliferating cell nuclear antigen (PCNA) and Bcl-2 expression, as well as reduced the expression level of p27, Bax and cleaved caspase-3. There are binding sites between miR-142-3p and FOXO1, which is miR-142-3p directly regulated FOXO1 expression. Moreover, above increases and decreases induced by miR-142-3p were attenuated by FOXO1 overexpression. In conclusion, miR-142-3p promotes the survival of pancreatic β cells through targeting FOXO1 in GDM. This study suggests that targeted regulation of miR-142-3p/FOXO1 might be a new strategy for the treatment of GDM.