A comparison between the effects of over-expression of miRNA-16 and miRNA-34a on cell cycle progression of mesothelioma cell lines and on their cisplatin sensitivity

Cancer Treat Res Commun. 2021:26:100276. doi: 10.1016/j.ctarc.2020.100276. Epub 2020 Dec 10.

Abstract

The prognosis of patients affected by malignant pleural mesothelioma (MPM) is presently poor and no therapeutic strategies have improved their survival yet. Introduction of miRNA mimics to restore their reduced or absent functionality in cancer cells is considered an important opportunity and a combination of miR's might be even more effective. In the present study, miR-16 and miR-34a were transfected, singularly and in combination, in MPM cell lines H2052 and H28, and their effects on cell proliferation and sensitivity to cisplatin are reported. Interestingly, the overexpression of both miRs, alone or combined, slows down the cell cycle progression, modulates the p53 and HMGB1 expression and increases the sensitivity of cells to cisplatin, producing a marked impairment of cell proliferation and strengthening the apoptotic effect of the drug. However, the co-overexpression of the two miRs results more effective only in the regulation of the cell cycle, but does not enhance the sensitivity of MPM cells to cisplatin. Consequently, although the potential of miR-16 and miR-34a is confirmed, we must conclude that their combination does not improve the response of MPM to chemotherapy.

Keywords: HMGB1; Mesothelioma; Transfection; miR-16; miR-34a.

MeSH terms

  • Apoptosis / genetics
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cisplatin / pharmacology*
  • Cisplatin / therapeutic use
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Regulation, Neoplastic
  • HMGB1 Protein / genetics
  • Humans
  • Mesothelioma, Malignant / drug therapy
  • Mesothelioma, Malignant / genetics*
  • Mesothelioma, Malignant / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Pleural Neoplasms / drug therapy
  • Pleural Neoplasms / genetics*
  • Pleural Neoplasms / pathology
  • Transfection
  • Tumor Suppressor Protein p53 / genetics

Substances

  • HMGB1 Protein
  • HMGB1 protein, human
  • MIRN16 microRNA, human
  • MIRN34 microRNA, human
  • MicroRNAs
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Cisplatin