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

Abstract

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.

Tanshinone II A enhances pyroptosis and represses cell proliferation of HeLa cells by regulating miR-145/GSDMD signaling pathway

“…In tumors, miRs can either function as tumor suppressor gene or oncogene by regulating downstream targets. It is reported that miR-145 was down-regulated in nasopharyngeal carcinoma [26], papillary thyroid carcinoma [27] and head and neck cancers [28]. For example, Liu et al [26] reported that miR-145 directed with CASC9, and the inhibition of miR-145 promoted cell migration and invasion but inhibited cell apoptosis in nasopharyngeal carcinoma cells, which provided a novel therapy for the treatment of nasopharyngeal carcinoma.…”

MicroRNA‐145 transcriptionally regulates Semaphorin 3A expression in prostate cancer cells

“…Bioinformatics analyses and in vitro studies have shown that p53 is a potential regulator of mir‐145, which has a putative p53 response element in its promoter (Kilic et al, 2019; Sachdeva et al, 2009). Upregulation of endogenous p53 has been reported to increase mir‐145 expression and its promoter activity in cancer cells (Sachdeva et al, 2009), implying a critical role for miR‐145 after loss of p53 activity during carcinogenesis processes (Fuchs, 2012; Sachdeva et al, 2009).…”

“…MicroRNAs are estimated to target and regulate the expression of about 60% of human genes (Shukla et al, 2011). They have been shown to be associated with the pathogenesis of various diseases including cancer, and can act as potential oncogenes or tumor suppressors, depending on the genes they are targeting (Kilic et al, 2019; Macharia et al, 2019).…”

Comprehensive in silico analysis for identification of novel candidate target genes, including DHX36, OPA1, and SENP2, located on chromosome 3q in head and neck cancers

“…Head and neck squamous cell carcinoma (HNSC), an aggressive malignant neoplasm, is one of the most frequent cancers in the head and neck region with a global annual incidence of 700 000 cases 1‐3 . Lifestyle habits, genetic risk factors, tobacco use, alcohol consumption, poor oral hygiene, and high‐risk human papilloma virus (HPV) infection are among the prominent risk factors for HNSC 4,5 .…”

“…Head and neck squamous cell carcinoma (HNSC), an aggressive malignant neoplasm, is one of the most frequent cancers in the head and neck region with a global annual incidence of 700 000 cases. [1][2][3] Lifestyle habits, genetic risk factors, tobacco use, alcohol consumption, poor oral hygiene, and high-risk human papilloma virus (HPV) infection are among the prominent risk factors for HNSC. 4,5 Despite improvements in the diagnostic and therapeutic modalities, there has been no remarkable increase in the overall survival rate of HNSC patients during the last few decades, 6 which is most probably due to the late stages at diagnosis and additional primary lesions.…”