摘要
目的探讨脱氢胆固醇还原酶7(7-dehydrocholesterol reductase,DHCR7)对结肠癌(colon cancer,CC)细胞增殖、凋亡、迁移和侵袭能力的影响及调控机制。方法利用生物信息学方法分析DHCR7表达与结肠癌癌免疫浸润、预后及抗肿瘤药物敏感度的关系。qRT-PCR、蛋白质印迹及IHC检测DHCR7的mRNA和蛋白表达水平。MTT和克隆形成实验、流式细胞术、细胞划痕和Transwell实验分别分析敲减DHCR7对细胞增殖的影响、细胞周期与凋亡、细胞迁移与侵袭的影响。通过基因富集分析筛选DHCR7调控的关键信号通路,并利用蛋白质印迹实验进行验证。结果生物信息学分析显示,DHCR7在结肠癌组织中高表达与结肠癌N分期、特异性生存期、无进展生存期、肿瘤免疫浸润水平及药物敏感度相关。在结肠癌组织和细胞系中,DHCR7表达上调。敲减DHCR7表达能够抑制HCT116细胞的增殖、迁移和侵袭。Wnt信号通路是DHCR7在CC中调控的关键信号通路之一,敲减DHCR7能够抑制Wnt信号通路。结论DHCR7调控Wnt信号通路促进结肠癌细胞EMT,从而促进HCT116细胞的增殖、迁移和侵袭。
Objective To explore the effects and regulatory mechanisms of dehydrocholesterol reductase 7(DHCR7)on the proliferation,apoptosis,migration,and invasion ability of colon cancer(CC)cells.Methods Using bioinformatics methods to analyze the relationship between DHCR7 expression and immune infiltration,prognosis,and sensitivity to anti-tumor drugs in colon cancer.qRT-PCR,Western blotting,and IHC were used to detect the mRNA and protein expression levels of DHCR7.Effect of DHCR7 knock-down on cell proliferation,cell cycle and apoptosis,cell migration and invasion was determined by MTT and colony formation assay,flow cytometry,wound-healing and Transwell assay,respectively.The key signaling pathways regulated by DHCR7 were screened out through gene enrichment analysis and validated by Western blotting.Results Bioinformatics analysis shows that the high expression of DHCR7 in colon cancer tissues was associated with the N-stage,specific survival,progression free survival,tumor immune infiltration level,and drug sensitivity of colon cancer.DHCR7 expression was upregulated in colon cancer tissues and cell lines.Knockdown of DHCR7 expression inhibited the proliferation,migration,and invasion of HCT166 cells.Wnt signaling pathway was one of the key signaling pathways regulated by DHCR7 in CC,and knockdown of DHCR7 inhibited Wnt signaling pathway.Conclusion DHCR7 regulates the Wnt signaling pathway to promote EMT in colon cancer cells,thereby promoting proliferation,migration,and invasion of HCT116 cells.
作者
白小岗
王延峰
刘永成
姬海涛
张静
BAI Xiaogang;WANG Yanfeng;LIU Yongcheng;JI Haitao;ZHANG Jing(School of Medicine,Yan’an University,Yan’an,Shaanxi,716000,China;Department of Endocrinology and Metabolism,Affiliated Hospital of Yan’an University,Yan’an,Shaanxi,716000,China;Department of Laboratory,Affiliated Hospital of Yan’an University,Yan’an,Shaanxi,716000,China;Department of Pathology,Affiliated Hospital of Yan’an University,Yan’an,Shaanxi,716000,China)
出处
《医学分子生物学杂志》
2025年第2期108-116,共9页
Journal of Medical Molecular Biology
基金
陕西省自然科学基础研究计划(No.2024JC-YBQN-0983)
中国高校产学研创新基金-华通国康医学科研资助项目(No.2023HT056)
延安市科技计划项目(No.2022SLSFGG-022)。
关键词
结肠癌
脱氢胆固醇还原酶7
细胞增殖
细胞迁移
WNT信号通路
colon cancer
7-dehydrocholesterol reductase
cell proliferation
cell migration
Wnt signaling pathway
