MiR-3940-5p Promotes Granulosa Cell Proliferation Through Targeting KCNA5 In Polycystic Ovarian Syndrome

Objectives:Polycystic ovary syndrome(PCOS),one of the most common endocrine abnormalities in reproductive-aged women,is characterized by the obligatory presence of hyperandrogenism,oligo-ovulation and/or polycystic ovaries,and represents one of the leading causes for anovulatory infertility.Increased granulosa cell(GC)proliferation may contribute to abnormal folliculogenesis in patients with polycystic ovary syndrome(PCOS),which affects approximately10% reproductive aged women.However,the mechanisms underlying increased GC proliferation in PCOS remain incompletely understood.Methods and Results:In this study,we identified miR-3940-5p as a hub miRNA in GC from PCOS using weighted gene co-expression network analysis(WGCNA),and real-time polymerase chain reaction(RT-PCR)analysis confirmed that miR-3940-5p was significantly increased in GC from PCOS.Enrichment analysis of predicted target genes of miR-3940-5p indicated potential roles of miR-3940-5p in follicular development and cell proliferation regulation.Consistently,functional study confirmed that miR-3940-5p overexpression promoted granulosa cell proliferation.Integrated analysis of m RNA expression profiling data and predicted target genes of miR-3940-5p identified potassium voltage-gated channel subfamily A member 5(KCNA5)as a potential target of miR-3940-5p,and was validated by luciferase reporter assay.Finally,functional analysis suggested KCNA5 expression was decreased in GC from PCOS and was directly inhibited by miR-3940-5p and KCNA5 downregulation mediated the proliferative role of miR-3940-5p,which suggested that miR-3940-5p promoted GC proliferation in a KCNA5 dependent manner.Conclusions:Our findings showed that miR-3940-5p was upregulated in GC from PCOS,and promoted cell proliferation through suppressing KCNA5 expression.These observations provided novel insight into the mechanism underlying increased granulosa cell proliferation in polycystic ovarian syndrome,and suggested that miR-3940-5p may represent a novel and promising target for improving GC function in PCOS.