miR-22 suppresses cell viability and EMT of ovarian cancer cells via NLRP3 and inhibits PI3K/AKT signaling pathway

Clin Transl Oncol. 2021 Feb;23(2):257-264. doi: 10.1007/s12094-020-02413-8. Epub 2020 Jun 10.

Abstract

Purpose: miR-22 plays a great role in inhibiting cell growth, metastasis and enhanced cell apoptosis in several cancers. The purpose of this study was to investigate the functions of miR-22 in ovarian cancer.

Methods: The proliferative ability was measured using CCK-8 assay. The protein expression associated with EMT and PI3K/AKT signaling biomarkers were measured by western blot. Luciferase assay applied to measure the luciferase activity. Kaplan-Meier method was performed to evaluate the overall survival rate of ovarian cancers.

Results: miR-22 was low expressed and NLRP3 was overexpressed in ovarian cancer tissues and cells, and downregulation of miR-22 was associated with poor prognosis. The expression of NLRP3 had a negative correlation with miR-22 expression in ovarian cancer. miR-22 promoted cell viability and EMT through directly binding to the 3'-UTR of NLRP3 mRNA and inhibited PI3K/AKT signaling pathway. NLRP3 partially restored functions of miR-22 on cell proliferation and EMT in ovarian cancer.

Conclusion: miR-22 impaired cell viability and EMT by NLRP3 and inhibited PI3K/AKT signaling pathway in ovarian cancer. The newly identified miR-22/NLRP3/PI3K/AKT axis provides novel insight into the pathogenesis of ovarian cancer.

Keywords: EMT; Ovarian cancer; PI3K/AKT; Viability; miR-22.

MeSH terms

  • 3' Untranslated Regions
  • Cell Proliferation / physiology
  • Cell Survival / physiology*
  • Down-Regulation
  • Epithelial-Mesenchymal Transition / physiology
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Luciferases / metabolism
  • MicroRNAs / physiology*
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Messenger / metabolism

Substances

  • 3' Untranslated Regions
  • MIRN22 microRNA, human
  • MicroRNAs
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • RNA, Messenger
  • Luciferases
  • Proto-Oncogene Proteins c-akt