Effect of inhibiting the expression of USP22 on cisplatin resistance in glioma cells

Objective To investigate the effects of inhibiting the expression of ubiquitin specific peptidase 22(USP22) on cisplatin resistance in glioma cells.

Methods The cisplatin-resistant glioma cell line(U251/CP2) was induced by gradual elevation of cisplatin concentration.The expression of USP22 in glioma cell line U251/CP2 was silenced using the transfection of USP22 small interfering RNA.The expression level of USP22 mRNA, cell apoptosis, viability and drug resistance index and protein level of USP22 were detected using RT-PCR, flow cytometry, CCK-8 and Western blotting, respectively.

Results The cisplatin-resistant glioma cell line of U251/CP2 and USP22 gene silencing cell lines of U251-shUPS22 and U251/CP2-shUSP22 were successfully constrcucted.The inhibition of USP22 expression could significantly increase the apoptosis rate of U251/CP2-shUSP22 cells(P < 0.01), and cisplatin could up-regulate the expression of USP22 protein in U251 and U251/CP2 cells(P < 0.01).The IC₅₀ values to cisplatin of U251-shUPS22, U251/CP2, U251/CP2-shUSP22 and U251 cells were (0.56±0.07)μg/mL, (73.73±2.74)μg/mL, (51.25±1.09)μg/mL and (1.23±0.13)μg/mL, respectively.

Conclusions The inhibition of USP22 expression can enhance the chemosensitivity to cisplatin in glioma cells, and reverse the resistance of cisplatin in resistant cell line.It is suggested that USP22 may be one of the potential molecular mechanisms of cisplatin resistance in glioma.