Affiliation: | 1. Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran Dental Research Center, Faculty of Dentistry, Islamic Azad University of Medical Sciences, Tehran, Iran;2. Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran Faculty of Dentistry, Islamic Azad University of Medical Sciences, Tehran, Iran;3. Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran Dental Materials Research Center, Dental School, Islamic Azad University of Medical Sciences, Tehran, Iran;4. Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran;5. School of Dentistry, Hormozgan University of Medical Sciences, Bandar Abbas, Iran;6. Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran Faculty of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran;7. Faculty of Dentistry, Zanjan University of Medical Sciences, Zanjan, Iran |
Abstract: | MicroRNA-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. |