LncRNA HOTAIRM1, miR-433-5p and PIK3CD function as a ceRNA network to exacerbate the development of PCOS

J Ovarian Res. 2021 Jan 23;14(1):19. doi: 10.1186/s13048-020-00742-4.

Abstract

Background: Currently, several non-coding RNAs (ncRNAs) were distinguished in polycystic ovarian syndrome (PCOS). This present study aims to explore the potential function of lncRNA HOTAIRM1/miR-433-5p/PIK3CD in ovarian granulosa cells.

Methods: We analyzed the expression profiles of HOTAIRM1, miR-433-5p and PIK3CD in PCOS samples by enquiring GEO database. GSEA was applied to enrich the pathways related to PCOS. The target association between HOTAIRM1 and miR-433-5p or the binding association between miR-433-5p and PIK3CD were assessed by online prediction tools and a dual luciferase reporter assay. qPCR and western blotting assays were used to detect PIK3CD expression after HOTAIRM1 and miR-433-5p treatment. The proliferation and apoptosis of ovarian granulosa cells were estimated by cell counting kit-8 and flow cytometry assays, respectively.

Results: The expression profiles of HOTAIRM1 and PIK3CD were increased, whereas miR-433-5p was decreased in PCOS tissues. PIK3CD expression was positively regulated by HOTAIRM1 and negatively modulated by miR-433-5p. Overexpression of HOTAIRM1 reduced the proliferative ability and increased the apoptotic ability of granulosa cells, whereas upregulation of miR-433-5p or downregulation of PIK3CD reversed the effects of HOTAIRM1 on granulosa cells. Moreover, overexpression of miR-433-5 displayed a results with increasing proliferative ability and decreasing apoptotic ability, but upregulation of PIK3CD eliminated the function of miR-433-5p on granulosa cells.

Conclusions: Our findings illustrated that HOTAIRM1 could sponge miR-433-5p to promote PIK3CD expression, thereby regulating the growth and apoptosis of granulose cells in PCOS.

Keywords: Apoptosis; Polycystic ovarian syndrome; Proliferation; ceRNA.

MeSH terms

  • Class I Phosphatidylinositol 3-Kinases / metabolism*
  • Female
  • Humans
  • MicroRNAs / metabolism*
  • Polycystic Ovary Syndrome / genetics*
  • Polycystic Ovary Syndrome / pathology
  • RNA, Long Noncoding / metabolism*

Substances

  • MIRN433 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CD protein, human