Mode of action of carboplatin via activating p53/miR-145 axis in head and neck cancers

Laryngoscope. 2020 Dec;130(12):2818-2824. doi: 10.1002/lary.28492. Epub 2019 Dec 30.

Abstract

Objectives: In this study, we aimed at investigating the expressions of miR-145 and its well-characterized direct targets on carboplatin treatment.

Study design: Laboratory study.

Methods: The effect of carboplatin and miR-145 on the proliferative capacity of head and neck squamous cell carcinoma cells was evaluated using Cell Viability Detection Kit-8. Expressions of miR-145 and its targets were evaluated using quantitative real-time polymerase chain reaction on carboplatin treatment and p53 inhibition. Western blot was used to measure the levels of p53 and its acetylated versions in cells treated with carboplatin and/or pifithrin-α.

Results: We demonstrated that carboplatin induced the expression of miR-145 in a dose-dependent manner and suppressed the expressions of miR-145 direct targets. In addition, we showed that inhibition of p53 by pifithrin-α in carboplatin-treated cells reduced miR-145 expression and reversed the suppression of miR-145 direct targets.

Conclusions: Considering all these findings together, one of the proposed mechanisms of carboplatin to kill cells might be the induction of miR-145 and deregulation of its targets in parallel, via p53 activation, which happens through carboplatin's DNA-damaging property. To the best of our knowledge, these findings are the first to reveal the relationship between carboplatin and miR-145 in cancer cells.

Level of evidence: NA Laryngoscope, 2019.

Keywords: Head and neck cancer; carboplatin; miR-145; microRNA; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzothiazoles / pharmacology
  • Blotting, Western
  • Carboplatin / pharmacology*
  • Carcinoma, Squamous Cell / drug therapy*
  • Cell Line, Tumor
  • Cell Proliferation
  • Head and Neck Neoplasms / drug therapy*
  • Humans
  • MicroRNAs / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toluene / analogs & derivatives
  • Toluene / pharmacology
  • Transfection
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Benzothiazoles
  • MIRN145 microRNA, human
  • MicroRNAs
  • Tumor Suppressor Protein p53
  • Toluene
  • Carboplatin
  • pifithrin