Circ_0070987 Promotes Pyroptosis of Ovarian Granulosa Cells in Polycystic Ovarian Syndrome Through the miR-139-5/CDH1 Axis.

Abstract

PCOS refers to an endocrine and metabolic disorder that affects female individuals of reproductive age. Our study explores the potential mechanism of circ_0070987 on PCOS in regulating pyroptosis of ovarian GCs, providing new evidence for PCOS treatment. PCOS cell model was established. The expression of circ_0070987, line ELF2, miR-139-5p and CDH1 was detected. Cell viability was measured. The expression of IL-1β, IL-18, NLRP3, cleaved Caspase-1, GSDMD-N, and CDH1 was analyzed. Circ_0070987 was downregulated to verify its effect on pyroptosis. The binding of miR-139-5p to circ_0070987 and CDH1 was verified by dual-luciferase report assay. The role of circ_0070987 in pyroptosis of ovarian GCs in PCOS through the miR-139-5p/CDH1 axis was validated. After DHT treatment, cell viability of SVOG was decreased, and the expression of IL-1β, IL-18, circ_0070987, NLRP3, cleaved Caspase-1 and GSDMD-N was increased. DHT-induced pyroptosis of ovarian GCs was inhibited upon circ_0070987 downregulation. Mechanistically, circ_0070987 negatively regulated miR-139-5p, which targeted and inhibited CDH1. Inhibitory effect of circ_0070987 downregulation on pyroptosis of ovarian GCs in PCOS was reduced after miR-139-5p downregulation or CDH1 overexpression. In conclusion, circ_0070987 inhibits miR-139-5p expression and upregulates CDH1 expression, thus promoting pyroptosis of ovarian GCs in PCOS.