Inhibition of hsa_circ_0003314 contributes to trophoblast cell migration and invasion and inhibits pyroptosis in preeclampsia.

Abstract

Inflammation is a key contributor to the development of preeclampsia. Recent studies suggest that circular RNAs (circRNAs) may serve as potential therapeutic targets for this disease, though their specific functions remain incompletely understood. In this study, we investigated the role of hsa_circ_0003314 in preeclampsia pathogenesis. The interaction between hsa_circ_0003314 and microRNA (miR)-1827 was validated using RNA pull-down and luciferase reporter assays, while the binding of miR-1827 to the 3'-UTR of caspase-5 was confirmed by RNA immunoprecipitation and luciferase reporter assays. Pyroptotic cells were quantified by flow cytometry based on the percentage of caspase-1/propidium iodide (PI) double-positive cells. Enzyme-linked immunosorbent assay (ELISA) was performed to measure interleukin (IL)-1β concentrations in the culture supernatant. The migration and invasion abilities of HTR-8/SVneo cells were evaluated using Transwell assays. We found that hsa_circ_0003314 expression was upregulated in HTR-8/SVneo cells subjected to hypoxia/reoxygenation (H/R) treatment. Silencing hsa_circ_0003314 enhanced cell migration, invasion, and epithelial-mesenchymal transition (EMT), while reducing the expression of pyroptosis-related proteins, GSDMD-N and HMGB1. The proportion of pyroptotic cells was significantly decreased upon hsa_circ_0003314 knockdown in H/R-treated cells. Mechanistically, hsa_circ_0003314 functions as a molecular sponge for miR-1827, thereby regulating caspase-5 expression. Notably, caspase-5 overexpression rescued the effects of hsa_circ_0003314 knockdown, restoring pyroptosis markers and suppressing the enhanced migratory and invasive behavior of HTR-8/SVneo cells. In conclusion, silencing hsa_circ_0003314 promotes migration, invasion, and EMT in H/R-treated HTR-8/SVneo cells by inhibiting caspase-5-mediated pyroptosis through the sequestration of miR-1827. These findings identify hsa_circ_0003314 as a promising therapeutic target in the treatment of preeclampsia.