MiR‐34 by targeting p53 induces apoptosis and DNA damage in paclitaxel‐resistant human oral squamous carcinoma cells

Abstract

AbstractMicroRNA‐34 (miR‐34) is one the most important tumor suppressor miRNAs involving in the various aspects of oral cancer. The present study aimed to evaluate the effects of miR‐34 restoration in OECM‐1 oral cancer resistant to paclitaxel (OECM‐1/PTX) and its underlying mechanisms through p53‐mediated DNA damage and apoptosis. OECM‐1 and OECM‐1/PTX were transfected with miR‐34 mimic and inhibitor. Cellular proliferation and apoptosis were evaluated through MTT assay and flow cytometry, respectively. The mRNA and protein expression levels of p53, p‐glycoprotein (P‐gp), ATM, ATR, CHK1, and CHK2 were assessed through qRT‐PCR and western blotting. Rhodamin123 uptake assay was used to measure the P‐gp activities. P53 expression was also suppressed by sing a siRNA transfection of cells. The expression levels of miR‐34 were downregulated in OECM‐1/PTX. Restoration of miR‐34 led to increase in cytotoxic effects of paclitaxel in cells. In addition, the expression levels and activities of P‐gp were reduced following miR‐34 transfection. miR‐34 transfection upregulated the p53, ATM, ATR, CHK1, and CHK2 expression levels in OECM‐1/PTX cells. Furthermore, cells transfected with miR‐34 showed higher levels of apoptosis. miR‐34 restoration reverses paclitaxel resistance in OECM‐1 oral cancer. The chemosensitive effects of miR‐34 is mediated through increasing DNA damage and apoptosis in a p53 depended manner.