【摘要】 目的 探讨微小染色体维持蛋白5(minichromosome maintenance proteins 5,MCM5)在乳腺癌中的表达及其生物学功能。方法 通过GEO数据库分析MCM5在乳腺癌及癌旁组织中的表达，并评估其与患者预后的相关性。收集2021—2023年在广西医科大学附属肿瘤医院治疗的乳腺癌患者的癌组织及其癌旁组织样本，体外培养乳腺癌细胞MDA-MB-231、MDA-MB-468及MCF-7和正常乳腺上皮细胞MCF-10A，采用免疫组化、RT-qPCR及Western blot检测组织及细胞中MCM5的表达水平。利用慢病毒介导的MCM5敲低细胞，采用EdU实验、克隆形成实验、划痕实验、Transwell侵袭实验及流式细胞术，检测MCM5对乳腺癌细胞增殖、迁移、侵袭及凋亡的影响。结果 GSE42568数据集分析显示，乳腺癌组织中MCM5的表达显著高于正常组织（P<0.0001），且高表达与患者较差的无病生存期和总生存期相关（均P<0.05）。免疫组化检测结果显示，MCM5在乳腺癌组织中的阳性表达率显著高于癌旁组织（53.13%vs16.76%,P<0.0001）。RT-qPCR和Western blot检测结果显示，MCM5在乳腺癌细胞中的mRNA和蛋白表达水平均高于正常乳腺细胞（均P<0.05）。功能实验显示，敲低MCM5后乳腺癌细胞的增殖、迁移和侵袭能力受到显著抑制（均P<0.05），而细胞凋亡水平显著增加（均P<0.05）。结论 MCM5在乳腺癌中高表达且与患者不良预后相关，敲低MCM5可抑制乳腺癌细胞增殖、侵袭和迁移，并诱导细胞凋亡。MCM5可能是乳腺癌治疗的新型潜在靶点。更多还原

【Abstract】 ObjectiveTo investigate the expression of minichromosome maintenance proteins 5(MCM5) in breast cancer and its biological functions.MethodsThe expression of MCM5 in breast cancer and para-cancerous tissues, along with its prognostic correlation,were analyzed by GEO database. Cancer tissue and para-cancerous tissue samples of breast cancer patients treated in Guangxi Medical University Cancer Hospital from 2021 to 2023 were collected. Breast cancer cells MDA-MB-231, MDA-MB-468 and MCF-7 and normal breast epithelial cells MCF-10A were cultured in vitro. The expression of MCM5 in tissues and cells were assessed by immunohistochemistry(IHC), RT-qPCR and Western blot. To investigate the effects of MCM5 on breast cancer cell proliferation, migration, invasion and apoptosis, lentivirus-mediated MCM5 knockdown cells were evaluated by EdU assay, colony formation, wound healing assay, Transwell invasion assay and flow cytometry.ResultsAnalysis of the GSE42568 dataset revealed that MCM5 expression was significantly higher in breast cancer tissues compared to normal tissues(P<0.001). Furthermore, high MCM5 expression was significantly associated with poorer disease-free survival and overall survival(all P<0.05). IHC results demonstrated that the positive expression rate of MCM5 in breast cancer tissues was significantly higher than that in para-cancer tissues(53.13% vs 16.76%, P<0.0001). RT-qPCR and Western blot analysis revealed that both the mRNA and protein expression levels of MCM5 were higher in breast cancer cells than in normal breast cells(all P<0.05). Functional assays revealed that MCM5 knockdown significantly inhibited breast cancer cell proliferation, migration and invasion,while increasing cell apoptosis(all P<0.05).ConclusionsMCM5 is highly expressed in breast cancer and is strongly associated with poor patient prognosis. MCM5 knockdown significantly inhibited the proliferation and migration of breast cancer cells and promoting apoptosis.MCM5 may serve as a novel and potential therapeutic target for breast cancer treatment.更多还原