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

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‐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