关键词: 宫颈鳞状细胞癌, 肥胖相关蛋白, FBXW7, m6A 甲基化, 放化疗抵抗

Abstract: Objective To investigate the effect of obesity-associated protein (FTO) and F-box and WD-40 domain protein 7 (FBXW7) on cervical squamous cell carcinoma (CSCC) radiotherapy and chemotherapy resistance. Methods Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to detect the expression levels of FTO and FBXW7 in CSCC cells. The TCGA (The Cancer Genome Atlas) data were used to analysis FTO and FBXW7 expression and correlation. FTO was overexpressed in CSCC cells, and immunoprecipitation was used to detect the changes in m6A expression of FBXW7. The MTT method was used to detect the role of FTO and FBXW7 in the resistance of CSCC cells to radiotherapy and chemotherapy. Results Compared with the human normal cervical epithelial cells (HUCEC), FTO and FBXW7 were weakly expressed in CSCC cells (SiHa, c-33a) (P < 0. 05). FTO regulated the m6A of FBXW7 mRNA. The cell survival ratio was decreased after the FTO-overexpressed CSCC cells were irradiated or treated with cisplatin (P< 0. 05). The inhibition of FBXW7 increased the cell survival ratio in irradiated or cisplatin treated FTO-overexpressed CSCC cells, which induced CSCC Chemo-Radiotherapy (P < 0. 05). Conclusion FTO could remove the m6A methylation modification of FBXW7, up-regulate the expression of FBXW7, and inhibit the resistance of CSCC to radiotherapy and chemotherapy. The effect of FTO on the malignant phenotype of CSCC was achieved through FBXW7. 

Key words: cervical squamous cell carcinoma, obesity-associated protein, F-box and WD-40 domain protein 7, m6A methylation, radiotherapy and chemotherapy resistance