中国肿瘤生物治疗杂志2025，Vol.32Issue(11)：1136-1142,7.DOI:10.3872/j.issn.1007-385x.2025.11.005
COX7A2敲低及其与顺铂联用对膀胱癌J82细胞增殖、凋亡及线粒体功能的影响
Effects of COX7A2 knockdown and its combination with cisplatin on the proliferation,apoptosis,and mitochondrial function of bladder cancer J82 cells
摘要
Abstract
Objective:To investigate cytochrome c oxidase subunit 7A2,mitochondrial(COX7A2)expression in bladder cancer cells,and the effects of its combination with cisplatin on the proliferation,apoptosis,and mitochondrial function of bladder cancer J82 cells.Methods:Bioinformatics analysis was used to assess COX7A2 expression in bladder cancer patients,with validation in the J82 cell.Functional experiments included four groups:the Control group(siNC transfection only),the siRNA group(COX7A2 siRNA transfection only),the Control+Cisplatin group(siNC transfection followed by cisplatin),and the siRNA+Cisplatin group(COX7A2 knockdown followed by cisplatin).CCK-8,Transwell migration assay,and colony formation assay detected the proliferation and migration abilities in the Control and siRNA groups.The ATP level,the ROS level,and MMP of cells in each group were detected using corresponding kits to assess mitochondrial function.Flow cytometry detected cell apoptosis in each group to reveal the responsive relationship between mitochondrial status and cisplatin treatment.Furthermore,the Cancer Treatment Response gene signature Database(CTR-DB)was utilized to analyze the correlation between COX7A2 expression and the prognosis of bladder cancer patients receiving cisplatin-based combination therapy.Results:Bioinformatics analysis and survival curves showed that COX7A2 was highly expressed in bladder cancer patients and was associated with poor prognosis.COX7A2 was significantly overexpressed in J82 cells(P<0.05).Without cisplatin treatment,compared with the Control group,the siRNA group exhibited significantly decreased abilities in the proliferation,migration,and colony formation of J82 cells(all P<0.001).Mitochondrial ATP expression decreased(P<0.01);ROS expression levels increased(P<0.000 1);MMP depolarized(P<0.000 1),and the apoptosis levels increased(P<0.05).After cisplatin treatment,compared with the Control+Cisplatin group,the siRNA+Cisplatin group showed decreased ATP expression(P<0.01),increased ROS expression levels(P<0.000 1),MMP depolarization(P<0.000 1),impaired mitochondrial function,and increased apoptosis levels(P<0.001).Bioinformatic analysis of the CTR-DB dataset indicated that among five bladder cancer patients receiving combination therapy of cisplatin,doxorubicin,methotrexate,and vincristine,responders had lower median COX7A2 RNA expression than non-responders(median expression:4 501 vs 5 009).Similarly,among 12 bladder cancer patients receiving platinum-based combination therapies,responders showed lower median COX7A2 RNA expression than non-responders(median expression:2 947 vs 3 035).However,due to the limited sample size,although a trend was observed,it did not reach statistical significance.Conclusion:Knockdown of COX7A2 can inhibit the proliferation and migration of bladder cancer cells by impairing mitochondrial function,and may thereby enhance cellular sensitivity to cisplatin-induced apoptosis.关键词
细胞色素c氧化酶亚基7A2/膀胱癌/线粒体损伤/顺铂/治疗反应Key words
cytochrome c oxidase subunit 7A2,mitochondrial(COX7A2)/bladder cancer/mitochondrial dysfunction/cisplatin/therapeutic response分类
医药卫生引用本文复制引用
王烜,张建敏,李海霞..COX7A2敲低及其与顺铂联用对膀胱癌J82细胞增殖、凋亡及线粒体功能的影响[J].中国肿瘤生物治疗杂志,2025,32(11):1136-1142,7.基金项目
国家自然科学基金(No.82472358) （No.82472358）
邯郸市科学技术研究与发展计划(No.21422083072) （No.21422083072）
