Overexpression of miR-144-3p alleviates polycystic ovaries syndrome through targeting expression of HSP-70

Gene Ther. 2022 May;29(5):217-226. doi: 10.1038/s41434-020-00191-0. Epub 2020 Sep 11.

Abstract

Increasing microRNAs are shown to be participate in polycystic ovarian syndrome (PCOS) pathogenesis. Nevertheless, the biological effects of miR-144-3p and its detailed mechanisms in PCOS are to be investigated. The purpose of our work was to study the function of miR-144-3p in PCOS. Currently, Expression of miR-144-3p was greatly reduced in PCOS patients and PCOS rat models. In addition, HSP-70 expression was greatly elevated PCOS. Cell proliferation assays and flow cytometry assay were carried out following the overexpression of miR-144-3p in ovarian granulosa cells from PCOS rat models. We observed that miR-144-3p overexpression induced the proliferation and repressed cell apoptosis while loss of miR-144-3p demonstrated an opposite process. Then, PCOS rat models were classified to four groups: LV-NC group, LV-miR-144-3p group, Anti-control group, and Anti-miR-144-3p group. In response to loss of miR-144-3p, we found E2, T, and LH serum levels were elevated and FSH serum level was inhibited. Upregulation of miR-144-3p exhibited an opposite process. Moreover, HSP-70 was a direct target of miR-144-3p. Furthermore, increased expression of HSP-70 rescued the effects of miR-144-3p on ovarian granulosa cell growth and apoptosis. In addition, knockdown of HSP-70 alleviated endocrine disorders and abnormal ovarian weight in vivo. To sum up, miR-144-3p might function as a novel target for PCOS treatment via targeting HSP-70.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Proliferation / genetics
  • Female
  • Granulosa Cells / metabolism
  • Granulosa Cells / pathology
  • HSP70 Heat-Shock Proteins
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Polycystic Ovary Syndrome* / genetics
  • Polycystic Ovary Syndrome* / metabolism
  • Polycystic Ovary Syndrome* / therapy
  • Rats

Substances

  • HSP70 Heat-Shock Proteins
  • MIRN144 microRNA, human
  • MIRN144 microRNA, rat
  • MicroRNAs