Curcumin inhibits ovarian cancer progression by regulating circ-PLEKHM3/miR-320a/SMG1 axis

J Ovarian Res. 2021 Nov 16;14(1):158. doi: 10.1186/s13048-021-00916-8.

Abstract

Background: Curcumin has a potential therapeutic role in ovarian cancer. However, whether curcumin plays anti-cancer role in ovarian cancer by mediating the circular RNA (circRNA)/microRNA (miRNA)/mRNA network is still unclear.

Methods: The expression of circ-PLEKHM3, miR-320a, and suppressor of morphogenesis in genitalia 1 (SMG1) was detected via qRT-PCR. Cell viability, colony-formation ability and apoptosis were analyzed via cell counting kit-8 assay, colony formation analysis, and flow cytometry. Protein expression was measured using western blot. The in vivo experiments were performed using a xenograft model. Target association was evaluated via dual-luciferase reporter analysis and RIP assay.

Results: Curcumin suppressed ovarian cancer cell proliferation and promoted apoptosis. Circ-PLEKHM3 was downregulated in ovarian cancer, and its expression could be promoted by curcumin treatment. Circ-PLEKHM3 overexpression exacerbated the effect of curcumin on ovarian cancer cell proliferation and apoptosis, as well as anti-tumor effect. MiR-320a was targeted by circ-PLEKHM3. The inhibition effect of circ-PLEKHM3 overexpression on cell proliferation and the enhancing effect on cell apoptosis could be reversed by miR-320a mimic. SMG1 was targeted by miR-320a, and its knockdown also reversed the regulation of miR-320a inhibitor on the proliferation and apoptosis of ovarian cancer cells. In addition, circ-PLEKHM3 could upregulate SMG1 expression via sponging miR-320a.

Conclusion: Curcumin restrained proliferation and facilitated apoptosis in ovarian cancer by regulating the circ-PLEKHM3/miR-320a/SMG1 axis.

Keywords: Circ-PLEKHM3; Curcumin; Ovarian cancer; SMG1; miR-320a.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Ovarian Epithelial / genetics*
  • Carcinoma, Ovarian Epithelial / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Proliferation / genetics
  • Curcumin / pharmacology*
  • Female
  • Humans
  • In Vitro Techniques
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Mice
  • Mice, Nude
  • MicroRNAs / drug effects*
  • MicroRNAs / genetics
  • Neoplasm Transplantation
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Protein Serine-Threonine Kinases / drug effects*
  • Protein Serine-Threonine Kinases / genetics
  • RNA, Circular / drug effects*
  • RNA, Circular / genetics

Substances

  • Antineoplastic Agents
  • Intracellular Signaling Peptides and Proteins
  • MIRN320 microRNA, human
  • MicroRNAs
  • PLEKHM3 protein, human
  • RNA, Circular
  • Protein Serine-Threonine Kinases
  • SMG1 protein, human
  • Curcumin