Hsa_circ_0063804 enhances ovarian cancer cells proliferation and resistance to cisplatin by targeting miR-1276/CLU axis

Aging (Albany NY). 2022 Jun 10;14(11):4699-4713. doi: 10.18632/aging.203474. Epub 2022 Jun 10.

Abstract

Purpose: This article researched circ_0063804 effects on ovarian cancer (OC) development and resistance to cisplatin, aiming to provide a new target for OC therapy.

Methods: A total of 108 OC patients participated in this study. The circle structure of circ_0063804 was investigated using RNase R. Circ_0063804 expression in OC cells were up-regulated or down-regulated by transfection. Cell proliferation was assessed by cell counting kit-8 assay and colony formation assay. Flow cytometry was used to detect apoptosis. OC cells resistance to cisplatin was explored through MTT assay. Luciferase reporter assay was performed. qRT-PCR and Western blot was applied to research genes expression. Xenograft tumor experiment was conducted using nude mice. Ki67 expression in xenograft tumor was detected by immunohistochemistry.

Results: Circ_0063804 expression was up-regulated in OC patients and indicated poor prognosis (P < 0.05). Circ_0063804 had a stable circle structure. Circ_0063804 enhanced proliferation, resistance to cisplatin and reduced apoptosis of OC cells (P < 0.01). miR-1276 was down-regulated in OC patients and sponged by circ_0063804. CLU was directly inhibited by miR-1276 and up-regulated in OC patients. Circ_0063804 exacerbated malignant phenotype and resistance to cisplatin of OC cells in vitro by enhancing CLU expression via sponging miR-1276 (P < 0.01). Circ_0063804 silencing inhibited OC cells growth, resistance to cisplatin and Ki67 expression in vivo (P < 0.01).

Conclusion: Circ_0063804 promoted OC cells proliferation and resistance to cisplatin by enhancing CLU expression via sponging miR-1276.

Keywords: OC; circ_0063804; drug resistance; miR-1276/CLU; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / genetics
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Clusterin
  • Female
  • Humans
  • Ki-67 Antigen
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics
  • RNA, Circular / genetics

Substances

  • CLU protein, human
  • Clusterin
  • Ki-67 Antigen
  • MIRN-1276 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Cisplatin