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Archive > Volume 33 Issue 8 > 2026,33(8):830-839. DOI:10.3872/j.issn.1007-385X.2026.08.003 Prev Next
Basic Research
RNF8 promotes DNA damage response through the ATM/CHK2 axis and affects cisplatin resistance in endometrial cancer cells
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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.
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