中国肿瘤生物治疗杂志2026，Vol.33Issue(8)：830-839,10.DOI:10.3872/j.issn.1007-385X.2026.08.003
RNF8通过ATM/CHK2轴促进DNA损伤应答并影响子宫内膜癌细胞顺铂抵抗性
RNF8 promotes DNA damage response through the ATM/CHK2 axis and affects cisplatin resistance in endometrial cancer cells
摘要
Abstract
Objective:To investigate the role of RING finger protein 8(RNF8)in cisplatin(CDDP)sensitivity in endometrial cancer(EC)and its possible mechanism.Methods:The expression level of RNF8 in endometrial cancer tissues and its copy number variation profile were analyzed using an online database.Lentivirus-mediated shRNA was used to stably knock down RNF8 expression in Ishikawa cells,followed by CDDP treatment.The cells were grouped:sh-NC+solvent control,sh-RNF8+solvent control,sh-NC+CDDP,and sh-RNF8+CDDP.An inhibition experiment was conducted using the sh-RNF8+CDDP+KU60019 combination.CCK-8 assays,colony formation assays,Annexin V-FITC/PI flow cytometry,Hoechst 33258/PI staining,WB,and γ-H2AX immunofluorescence were used to assess cell viability,colony formation,apoptosis,DNA damage,and the expression of proteins related to the ATM/CHK2 pathway.Results:RNF8 was significantly overexpressed in endometrial cancer tissues and cells.RNF8 knockdown reduced cell viability and IC50,inhibited colony formation,and further enhanced CDDP-induced apoptosis.Meanwhile,the expression of BAX,Cleaved-Caspase-3,and γ-H2AX increased,while the expression of BCL-2,p-ATM,p-CHK2,and RAD21 decreased.Treatment with KU60019 further promoted DNA damage and apoptosis,and reduced cell viability.Conclusion:RNF8 may promote DNA damage response and reduce the sensitivity of endometrial cancer cells to CDDP via the ATM/CHK2 axis.Knocking down RNF8 increases DNA damage and enhances sensitivity to CDDP.关键词
环指蛋白8/DNA损伤应答/ATM/CHK2信号通路/顺铂Key words
RING finger protein 8(RNF8)/DNA damage response/ATM/CHK2 pathway/cisplatin(CDDP)分类
医药卫生引用本文复制引用
蔡菲菲,杨婷婷,邵洋,马新,强萍,赵芳,奚星澍..RNF8通过ATM/CHK2轴促进DNA损伤应答并影响子宫内膜癌细胞顺铂抵抗性[J].中国肿瘤生物治疗杂志,2026,33(8):830-839,10.基金项目
江苏省妇幼健康科研项目(F202167) （F202167）
