Exploring the Mechanism of MicroRNA-125a Reversing the Resistance of Laryngeal Cancer Stem Cells to Cisplatin from Mitochondrial Autophagy

Abstract

To explore the mechanism of microRNA-125a reversing the resistance of laryngeal cancer stem cells to cisplatin from mitochondrial autophagy. The human laryngeal carcinoma cell line Hep-2 was purchased from Shanghai Bioleaf Biotechnology Co., Ltd. The expression of microRNA-125a messenger RNA in each group of cells was analyzed by reverse transcription-polymerase chain reaction. The cell migration and invasion ability of each group was evaluated by Transwell assay. Cell apoptosis was detected by flow cytometry. Western blot analysis was conducted to evaluate the protein expression. The expression of microRNA-125a messenger RNA in the Hep-2/diamminedichloroplatinum group was lower than that in the control group (p<0.05) and the expression of microRNA-125a messenger RNA in the microRNA-125a mimic group was higher than that in the Hep-2/diamminedichloroplatinum group (p<0.05). Compared with the Hep-2/diamminedichloroplatinum group, the microRNA-125a mimic group had more mitochondrial fragments and the average branch length of mitochondria decreased (p<0.05). The cell migration, invasion and viability of the Hep-2/diamminedichloroplatinum group increased (p<0.05) and the apoptosis rate decreased (p<0.05). The protein expression of phosphoinositide 3-kinase, protein kinase B and mammalian target of rapamycin in the Hep-2/diamminedichloroplatinum group was higher than that in the control group (p<0.05) and their expression in the microRNA-125a mimic group was lower than that in the Hep-2/ diamminedichloroplatinum group (p<0.05). The dysregulation of microRNA-125a was related to diamminedichloroplatinum resistance in laryngeal cancer and diamminedichloroplatinum resistance was induced by microRNA-125a through phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathway mediated autophagy inhibition. Overexpression of microRNA-125a inhibited the growth and metastasis of Hep-2/diamminedichloroplatinum cells through the phosphoinositide 3-kinase/ protein kinase B/mammalian target of rapamycin pathway and induced their apoptosis and autophagy.