High glucose suppresses the viability and proliferation of HTR-8/SVneo cells through regulation of the miR-137/PRKAA1/IL-6 axis

The aim of the present study was to investigate the mechanism underlying the high glucose (HG)-associated regulation of HTR-8/SVneo cell viability and proliferation during gestational diabetes mellitus (GDM), and to verify the association of microRNA (miR)-137, protein kinase AMP-activated catalytic subunit α1 (PRKAA1) and interlukin-6 (IL-6). miR-137-overexpressing and negative control HTR-8/SVneo cells were established by lentiviral vector infection. Cell Counting Kit-8 and colony formation assays were used to analyze the viability and proliferation of HTR-8/SVneo cells. Reverse transcription-quantitative polymerase chain reaction analysis was used to determine the transcriptional activity of miR-137, PRKAA1 and Il-6, and ELISA and western blot analysis were used to measure the protein levels of IL-6 and PRKAA1, respectively. It was demonstrated that PRKAA1 was decreased in the placental tissues of women with GDM and HG-treated HTR-8/SVneo cells, and that HG upregulated miR-137 and IL-6 in trophoblasts. The overexpression of miR-137 decreased levels of PRKAA1 and increased levels of IL-6 in the HTR-8/SVneo cells. An inhibitor of PRKAA1 promoted the secretion of IL-6, whereas an agonist of PRKAA1 suppressed the production of IL-6. HG treatment and the overexpression of miR-137 reduced the viability and proliferation of HTR-8/SVneo cells in vitro, whereas the activation of PRKAA1 or incubation with IL-6 antibody reversed these effects. Overall, it was concluded that HG suppressed the viability and proliferation of trophoblast cells through the miR-137/PRKAA1/IL-6 axis, which may contribute to pathological changes of placental tissues in GDM.