MiR-1224-5p attenuates polycystic ovary syndrome through inhibiting NOD-like receptor protein 3 inflammasome activation via targeting Forkhead box O 1

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that poses a great threat to women's health. MiR-1224-5p is downregulated in the follicular fluid of patients with PCOS, but its role remains largely unknown. In this study, mice were treated with dehydroepiandrosterone (DHEA) to establish an <i>in vivo</i> model of PCOS. We found that enhanced activation of NLRP3 inflammasome was accompanied by downregulation of miR-1224-5p in ovarian tissue of PCOS mice. The effect of miR-1224-5p was further explored in TNF-α-treated human granulosa-like tumor (KGN) cells. Upregulation of miR-1224-5p suppressed TNF-α-induced secretion of DHEA and testosterone. MiR-1224-5p attenuated TNF-α-induced inflammation by inhibiting NLRP3 inflammasome activation, IL-1β synthesis, and nuclear factor kappa B (NF-κB) p65 nuclear translocation. Notably, miR-1224-5p decreased the expression of Forkhead box O 1 (FOXO1) and its downstream gene thioredoxin interaction protein (TXNIP). Luciferase reporter assay confirmed FOXO1 as a target of miR-1224-5p. Upregulation of FOXO1 abolished miR-1224-5p-induced activation of NLRP3 inflammasome, demonstrating that miR-1224-5p might inhibit NLRP3 inflammasome activation through regulating FOXO1. This study provided novel insights into the pathogenesis of PCOS and suggested that miR-1224-5p might be a promising target for treating PCOS.