Stem cell transcription factor OCT4 promotes cisplatin resistance in gastric cancer by upregulating DNA methyltransferase 1 (DNMT1)

Abstract

Abstract Purpose To investigate the stem cell transcription factor OCT4 up-regulating DNA methyltransferase 1 (DNMT1) in the regulation of cisplatin (CDDP) resistance in gastric cancer (GC). Methods Human GC cell lines HGC-27 and MGC-803 were transfected with specific small interfering fragment siRNA-OCT4 to construct interfering cell lines. γ-H2AX immunofluorescence was used to detect DNA damage. The protein expressions of OCT4 and DNMT1 were detected by western blot and the effect of CDDP treatment on cell apoptosis and proliferation was detected by CCK8, cell cloning and flow cytometry. Results There is a targeted regulatory relationship between OCT4 and DNMT1. The expression of OCT4 and DNMT1 were significantly increased in CDDP induced cells, and the expression of DNMT1 was decreased in siRNA-OCT4 group. Compared with the siRNA-OCT4 group, the apoptosis of cells in the siRNA-OCT4 + CDDP group was increased, and the proliferation ability was decreased. Overexpression of DNMT1 reversed the effect of OCT4 on cisplatin sensitivity of gastric cancer cells. Conclusions The increased expression of OCT4 and the up-regulating of DNMT1 is associated with CDDP resistance in gastric cancer cells. Overexpression of OCT4 promoted DNMT1 expression and GC cell proliferation, induced cell apoptosis, and reduced CDDP resistance.