Investigation of the anti-cancer effects of carboplatin on head and neck cancer cells in association with MiR-145

Head and neck squamous cell carcinoma (HNSCC) is one of common cancer types in the head and neck region. Carboplatin is used against several cancers including HNSCC. Carboplatin has been shown to change microRNA profile of tumor cells, however, there is limited study about the involvement of microRNAs while carboplatin exerts its cytotoxic effects. In this study, we aimed at investigating the expressions of miR-145 and its well-characterized direct-targets upon carboplatin treatment. The effects of carboplatin and miR-145 on the proliferative capacity of HNSCC cells were evaluated using Cell Viability Detection Kit-8. Expressions of miR-145 and its targets were evaluated using quantitative-real-time-PCR upon 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. We demonstrated that carboplatin inhibited the viability of HNSCC cells and induced the expression of miR-145 in a dose dependent manner. Similar to miR-145 overexpression, carboplatin treatment suppressed the expressions of miR-145 direct-targets. Besides, we showed that carboplatin activated p53, which is a transcriptional activator of miR-145, and inhibition of p53 by pifithrin-α in carboplatin-treated cells reversed the suppression of miR-145 direct-targets. Our results show that one of the mechanisms of carboplatin to kill cells might be 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.