RRC ID 83627
Author Zhang H, Fang J, Liu Y, Zhu W, Xu Y, Zhang Y, Shen W, Li D, Hao C.
Title Hsa_circ_0043532 contributes to PCOS through upregulation of CYP19A1 by acting as a ceRNA for hsa-miR-1270.
Journal J Ovarian Res
Abstract BACKGROUND:Polycystic ovarian syndrome (PCOS) accounts for about 75% of anovulatory infertility. The cause of PCOS is not clear. CircRNAs acting as miRNA sponges mediate the post-transcriptional regulation of multiple genes. CYP19A1 is a limiting enzyme in the ovarian steroidogenesis pathway. However, the mechanism of circRNAs regulating granulosa cell (GC) estradiol secretion in PCOS remains to be elucidated.
METHODS:Bioinformatics was used to predict the potential target miRNAs of circ_0043532 and target genes of miR-1270. Target miRNAs and mRNA expression were verified by qRT-PCR in GCs from 45 women with PCOS and 65 non-PCOS. Western blot, ELISA and dual-luciferase reporter assays were applied to confirm the substrate of miR-1270.
RESULTS:Circ_0043532 and CYP19A1 were significant up-regulation in GCs from patients with PCOS. The predicted target miRNAs of circ_0053432, miR-1270, miR-576-5p, miR-421 and miR-142-5p, were notably decreased in GCs from patients with PCOS. Mechanistic experiments showed that circ_0043532 specifically binds to miR-1270. MiR-1270 was negatively regulated by circ_0043532. Concomitantly, miR-1270 inhibited CYP19A1 expression and estradiol production, which could be reversed by circ_0043532 over-expression.
CONCLUSION:We identified that circ_0043532/miR-1270/CYP19A1 axis contributes to the aberrant steroidogenesis of GCs from patients with PCOS. This study broadens the spectrum of pathogenic factors of PCOS, and circ_0043532 might be a potential therapeutic target for PCOS.
Volume 17(1)
Pages 151
Published 2024-7-22
DOI 10.1186/s13048-024-01474-5
PII 10.1186/s13048-024-01474-5
PMID 39039600
PMC PMC11265019
MeSH Adult Aromatase* / genetics Aromatase* / metabolism Female Granulosa Cells / metabolism Humans MicroRNAs* / genetics MicroRNAs* / metabolism Polycystic Ovary Syndrome* / genetics Polycystic Ovary Syndrome* / metabolism RNA, Circular* / genetics RNA, Circular* / metabolism RNA, Competitive Endogenous Up-Regulation*
IF 2.469
Resource
Human and Animal Cells KGN(RCB1154)