circVEGFC strengthens high glucose-induced trophoblast cell inflammation and apoptosis.

Gestational diabetes mellitus (GDM) is caused by impaired glucose tolerance at pregnancy. circVEGFC is highly expressed in GDM, but its specific regulatory mechanisms remain unclear. This study is the first to explore the role of circVEGFC in high glucose (HG)-induced trophoblast cell inflammation and apoptosis, aiming to provide a new target for GDM. HTR8/SVneo cells were treated by HG to establish GDM models, followed by transfection with sh-circVEGFC to silence circVEGFC expression. Cell viability, apoptosis and inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-10) were determined. Furthermore, the binding relation between circVEGFC and miR-30d-5p and between miR-30d-5p and Caspase-3 were verified. Co-transfection experiments with si-VEGFC, miR-30d-5p inhibitor, or oe-Caspase-3 were performed to clarify the regulatory axis. circVEGFC was overexpressed in HG-induced HTR8/SVneo cells, and circVEGFC knockout reduced cell inflammatory reaction and apoptosis, elevated miR-30d-5p expression and inactivated Caspase-3. Functionally, circVEGFC acted as a molecular sponge for miR-30d-5p, which targeted and repressed Caspase-3 expression. miR-30d-5p knockout and Caspase-3 overexpression could reverse the protective effect of circVEGFC silencing on HG-induced trophoblast cell apoptosis and inflammatory injury. In conclusion, circVEGFC exacerbates HG-induced trophoblast cell inflammation and apoptosis through the miR-30d-5p/Caspase-3 axis in a ceRNA-dependent manner.