MiR-3940-5p promotes granulosa cell proliferation through targeting KCNA5 in polycystic ovarian syndrome

Biochem Biophys Res Commun. 2020 Apr 16;524(4):791-797. doi: 10.1016/j.bbrc.2020.01.046. Epub 2020 Feb 1.

Abstract

Increased granulosa cell (GC) proliferation may contribute to abnormal folliculogenesis in patients with polycystic ovary syndrome (PCOS), which affects approximately 10% reproductive aged women. However, the mechanisms underlying increased GC proliferation in PCOS remain incompletely understood. 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 mRNA 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 that miR-3940-5p promoted GC proliferation in a KCNA5 dependent manner. In conclusion, miR-3940-5p was a hub miRNA upregulated in GC from PCOS, and promoted GC proliferation by targeting KCNA5.

Keywords: Cell proliferation; Granulosa cell; MicroRNA; Polycystic ovary syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antagomirs / genetics
  • Antagomirs / metabolism
  • Cell Proliferation
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Ontology
  • Gene Regulatory Networks
  • Genes, Reporter
  • Granulosa Cells / metabolism*
  • Granulosa Cells / pathology
  • Humans
  • Kv1.5 Potassium Channel / antagonists & inhibitors
  • Kv1.5 Potassium Channel / genetics*
  • Kv1.5 Potassium Channel / metabolism
  • Luciferases / genetics
  • Luciferases / metabolism
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Molecular Sequence Annotation
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Polycystic Ovary Syndrome / genetics*
  • Polycystic Ovary Syndrome / metabolism
  • Polycystic Ovary Syndrome / pathology
  • Primary Cell Culture
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction

Substances

  • Antagomirs
  • KCNA5 protein, human
  • Kv1.5 Potassium Channel
  • MIRN3940 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Small Interfering
  • Luciferases