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TM6SF1基因在肺腺癌细胞中的作用 被引量:1
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作者 刘婷隽 《黑龙江医学》 2023年第23期2837-2840,共4页
目的:探讨TM6SF1基因在肺腺癌细胞中的作用。方法:通过GEPIA数据库分析TM6SF1基因在肺腺癌及正常组织中的表达情况;细胞增殖实验检测过表达TM6SF1后,A549细胞的增殖情况;细胞划痕实验检测过表达TM6SF1后,A549细胞伤口愈合情况;Transwel... 目的:探讨TM6SF1基因在肺腺癌细胞中的作用。方法:通过GEPIA数据库分析TM6SF1基因在肺腺癌及正常组织中的表达情况;细胞增殖实验检测过表达TM6SF1后,A549细胞的增殖情况;细胞划痕实验检测过表达TM6SF1后,A549细胞伤口愈合情况;Transwell细胞实验检测过表达TM6SF1后,A549细胞侵袭和迁移情况。结果:通过GEPIA数据库分析得知,与正常组织相比,TM6SF1在肺腺癌中的表达降低,差异有统计学意义(^(*)P<0.05,^(**)P<0.01,^(***)P<0.001),且高表达TM6SF1组生存期更长。另外,TM6SF1与细胞增殖相关的核抗原Ki-67具有负相关性。过表达TM6SF1后,A549细胞的增殖,侵袭和迁移都受到抑制,差异有统计学意义(^(*)P<0.05,^(**)P<0.01,^(***)P<0.001),且下调细胞中信号(PI3K/Akt)通路相关激酶的表达。结论:TM6SF1基因在肺腺癌中可能作为抑癌因子。 展开更多
关键词 肺腺癌细胞 tm6sf1基因 增殖 迁移 侵袭
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TM6SF1通过抑制KRAS-MEK-ERK信号通路影响肝内胆管癌细胞的生物学行为
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作者 陈顺琦 刘信燚 +5 位作者 曾涛 刘梦玉 王玉婷 辛海贝 李元丰 周钢桥 《中国癌症防治杂志》 CAS 2024年第3期261-270,共10页
目的探究六次跨膜蛋白1(transmembrane 6 superfamily member 1,TM6SF1)在肝内胆管癌(intrahepatic cholangiocarcinoma,iCCA)中的生物学行为及其作用机制。方法收集2008年8月至2012年12月于东方肝胆外科医院(中国上海)收治的26例iCCA... 目的探究六次跨膜蛋白1(transmembrane 6 superfamily member 1,TM6SF1)在肝内胆管癌(intrahepatic cholangiocarcinoma,iCCA)中的生物学行为及其作用机制。方法收集2008年8月至2012年12月于东方肝胆外科医院(中国上海)收治的26例iCCA患者肿瘤组织及相应癌旁正常组织。采用RT-qPCR分析TM6SF1 mRNA表达情况;下载FU-iCCA队列iCCA患者的临床数据和肿瘤组织mRNA测序数据,分析TM6SF1与iCCA患者的临床特征以及KRAS-MEK-ERK信号通路相关分子的相关性,并进行通路富集分析;基于TCGA数据库,采用Log-rank分析TM6SF1的表达水平与患者预后的关系。利用瞬时转染技术在人源肝胆管癌细胞系RBE、HCCC-9810中构建瞬时敲低或过表达TM6SF1的肝胆管癌细胞株。采用CCK-8、平板克隆形成、Transwell实验评估TM6SF1对RBE、HCCC-9810细胞增殖、迁移和侵袭能力的影响。采用流式细胞术实验评估TM6SF1对RBE、HCCC-9810细胞周期和凋亡的影响。采用Ras活性检测实验检测GTP-RAS活性。采用Western blot法检测信号通路节点分子的表达情况。结果相比于癌旁组织,TM6SF1 mRNA表达水平在iCCA癌组织中显著下调(P<0.001),且TM6SF1低表达的iCCA患者其肿瘤恶性程度更高,总生存率和无病生存率更低(均P<0.05)。敲低TM6SF1促进RBE、HCCC-9810细胞的增殖、迁移与侵袭能力,抑制细胞凋亡(均P<0.01);而过表达TM6SF1抑制RBE、HCCC-9810细胞的增殖、迁移与侵袭能力,促进细胞凋亡(均P<0.05),但均不影响细胞周期。基于FU-iCCA队列mRNA测序数据的通路富集分析显示,TM6SF1低表达与KRAS信号通路的激活相关。RBE和HCCC-9810细胞中敲低TM6SF1可增强GTP-RAS活性,上调p-MEK和p-ERK的蛋白表达(均P<0.001);而过表达TM6SF1可抑制GTP-RAS活性,下调p-MEK和p-ERK的蛋白表达(均P<0.01)。使用KRAS激动剂KRA-533处理瞬时过表达TM6SF1的细胞株后GTP-RAS、p-MEK、p-ERK蛋白表达水平均增加(均P<0.05)。结论TM6SF1可能通过抑制KRAS-MEK-ERK信号通路抑制iCCA细胞的增殖、迁移与侵袭能力,促进细胞凋亡,并且TM6SF1的低表达与iCCA的不良预后相关。 展开更多
关键词 肝内胆管癌 tm6sf1 增殖 迁移 侵袭 凋亡 KRAS
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TM4SF1 as a Prognostic Biomarker and Therapeutic Target in Cervical Cancer
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作者 Jue-xiao Deng Lan-yue Zhang +3 位作者 Zhu-qing Ouyang Ting Guo Fu-jin Shen Hong-yun Zheng 《Current Medical Science》 2025年第6期1367-1381,共15页
Objective Accumulating evidence suggests that transmembrane 4 L6 family member 1(TM4SF1)is associated with the development of various cancers;yet comprehensive studies on TM4SF1 in cervical cancer are lacking.Therefor... Objective Accumulating evidence suggests that transmembrane 4 L6 family member 1(TM4SF1)is associated with the development of various cancers;yet comprehensive studies on TM4SF1 in cervical cancer are lacking.Therefore,we aimed to evaluate the prognostic value of TM4SF1 in cervical cancer,elucidate its potential oncogenic functions in this disease,and further explore its feasibility as a therapeutic target.Methods The expression profiles and clinical information of cervical cancer patients were obtained from The Cancer Genome Atlas(TCGA)database.The expression levels of TM4SF1 were compared between cervical cancer and normal cervical tissues using the Wilcoxon rank-sum test.Kaplan–Meier analysis was employed to assess the prognostic value of TM4SF1.Furthermore,functional enrichment analyses were performed to explore the associated signaling pathways and biological functions.The methylation status of TM4SF1 was analyzed using the UALCAN and MethSurv databases.In addition,in vitro experiments were conducted to preliminarily validate the role and mechanisms of TM4SF1 in cervical cancer.Results TM4SF1 was overexpressed in nearly all tumors,and its overexpression was associated with poor prognosis in cervical cancer.Moreover,the correlation between TM4SF1 expression and the expression of immune cell infiltration markers and immune checkpoint genes suggested that it had potential applications in cancer immunotherapy.Western blot analysis and immunohistochemistry revealed significantly elevated protein levels of TM4SF1 in cervical cancer tissues and cells.Further studies revealed that the knockdown of TM4SF1 significantly inhibited the migration,invasion,and epithelial-mesenchymal transition(EMT)of HeLa and SiHa cells,as well as promoted their apoptosis.Conclusion TM4SF1 may serve as a potential prognostic biomarker and therapeutic target for cervical cancer. 展开更多
关键词 Transmembrane 4 L6 family member 1(TM4SF1) Cervical cancer BIOMARKER Therapeutic target Invasion and migration Epithelial-mesenchymal transition(EMT) IMMUNOTHERAPY DNA methylation
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