MiR-181a Promotes Apoptosis and Reduces Cisplatin Resistance by Inhibiting Osteopontin in Cervical Cancer Cells

Cancer Biother Radiopharm. 2019 Nov;34(9):559-565. doi: 10.1089/cbr.2019.2858. Epub 2019 Aug 22.

Abstract

Objective: In this study, the authors established a cervical cancer cisplatin (DDP) drug-resistant cell line to explore the role of miR-181a in the regulation of osteopontin (OPN) expression and the proliferation, apoptosis, as well as DDP resistance of cervical cancer cells. Materials and Methods: Dual luciferase reporter gene assay was performed to validate the targeted relationship between miR-181a and OPN. The DDP-resistant cell line CaSki/DDP was established to compare the expressions of miR-181a and OPN. The cell proliferation activity was detected by CCK-8 assay. CaSki/DDP cells were divided into miR-NC group and miR-181a mimic group followed by analysis of cell apoptosis by flow cytometry, and the cell proliferation by EdU staining. Results: There was a targeted relationship between miR-181a and OPN mRNA. MiR-181a expression was significantly lower, while OPN mRNA and protein levels were significantly higher in CaSki/DDP cells than that in CaSki cells. Compared with the miR-NC group, OPN mRNA and protein were significantly decreased, cell apoptosis was significantly increased, and cell proliferation ability was significantly attenuated in miR-181a mimic transfection group. Conclusions: The decrease of miR-181a expression and the upregulation of OPN expression are related to the DDP resistance of cervical cancer cells. Overexpression of miR-181a can inhibit the expression of OPN, induce cell apoptosis cells, restrain cell proliferation, and reduce DDP resistance in cervical cancer cells.

Keywords: DDP; OPN; cervical cancer; drug resistance; miR-181a.

Publication types

  • Retracted Publication

MeSH terms

  • 3' Untranslated Regions
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / genetics*
  • Cell Line
  • Cell Proliferation
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • Mutation
  • Osteopontin / genetics*
  • Osteopontin / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology

Substances

  • 3' Untranslated Regions
  • Antineoplastic Agents
  • MIrn181 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • SPP1 protein, human
  • Osteopontin
  • Cisplatin