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.