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

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-alpha. 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-alpha 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