Investigating the role of miR-532-5p in overcoming cisplatin drug resistance through ZNRD1/MDR1/p-gp pathway in patients with osteosarcoma

Abstract

Recently, various studies have focused on the therapeutic potential of miRNAs, especially miR-532-5p, which is one of the tumor suppressor miRNAs, in various human malignancies, including osteosarcoma. However, the underlying mechanisms in the anticancer effects mediated by miR-532-5p are still not fully understood. Therefore, the present study investigated the effect of miR-532-5p on cisplatin-induced apoptosis (CIS) in MG-63 cells and resistant cells. Methods: MG-63 and MG-63/CIS cells were treated with CIS, miR-532-5p and a combination of both, and cell viability was evaluated by MTT method. The expression of miR-532-5p, ZNRD1 and MDR1 was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Flow cytometry method was also used to investigate apoptosis. Results: As expected, miR-532-5p was less expressed in MG-63/CIS cells (P<0.05). Overexpression of miRNA-205 was shown to significantly inhibit the viability of MG-63/CIS cells. Increased expression of miR-532-5p significantly decreased the expression and activity of MDR1 in CIS-resistant cells (P<0.05). Expression of miR-532-5p led to downregulation of ZNRD1 and sequentially lower expression of MDR1, which reversed drug resistance. Also, overexpression of miR-532-5p increased the apoptosis rate of MG-63/CIS cells.