为了研究KLF基因家族成员在乳腺癌发生中的分子机制及其与患者预后的关系,我们利用GEPIA对KLF家族进行Kaplan-Meier生存分析,筛选出与患者预后显著相关家族成员;在Oncomine数据库中分析前面筛选出的与乳腺癌预后有关的KLF家族成员;采用c...为了研究KLF基因家族成员在乳腺癌发生中的分子机制及其与患者预后的关系,我们利用GEPIA对KLF家族进行Kaplan-Meier生存分析,筛选出与患者预后显著相关家族成员;在Oncomine数据库中分析前面筛选出的与乳腺癌预后有关的KLF家族成员;采用c Bio Portal筛选出与患者预后有关的KLF家族成员共表达基因;STRING构建蛋白互作网络,Cytoscape软件中的MCODE插件识别网络模块,再用STRING对网络模块进行聚类分析。Kaplan-Meier生存分析显示KLF家族成员中KLF13和KLF15与乳腺癌预后显著相关（p〈0.05）;Oncomine分析显示只有KLF13在乳腺癌组织表达显著高于正常组织（p〈0.01）;c Bio Portal中筛选出KLF13共表达基因274个;Cytoscape软件中的MCODE插件识别出网络模块3个,STRING进行GO分析发现,网络模块中基因主要参与线粒体内的翻译和呼吸链氧化磷酸化生成ATP等生物过程,KEGG分析发现网络模块中涉及基因主要线粒体蛋白质翻译场所核糖体及其氧化磷酸化等信号通路有关。以上表明KLF13可能通过线粒体信号通路来影响乳腺癌的发生,可作为一个候选的乳腺癌临床预后标志物和潜在的治疗靶点。展开更多
Background and Aims:Krüppel-like factor(KLF)has a role in the occurrence,development and metabolism of can-cer.We aimed to explore the role and potential molecular mechanism of KLF13 in the growth and migration o...Background and Aims:Krüppel-like factor(KLF)has a role in the occurrence,development and metabolism of can-cer.We aimed to explore the role and potential molecular mechanism of KLF13 in the growth and migration of liver cancer cells.Methods:The expression of KLF13 in hepa-tocellular carcinoma(HCC)tissues was higher than that in normal tissues according to analysis of The Cancer Genome Atlas(TCGA)database.Lentiviral plasmids were used for overexpression and plasmid knockdown of KLF13.Real-time quantitative polymerase chain reaction(qPCR)and western blotting were used to detect mRNA and protein expression in HCC tissues and cells.Cell counting kit-8(CCK-8),colony formation,cell migration and invasion,and flow cytometry assays were used to assess the in vitro function of KLF13 in HCC cells.The effect of KLF13 on xenograft tumor growth in vivo was evaluated.The cholesterol content of HCC cells was determined by an indicator kit.A dual-luciferase reporter assay and chromatin immunoprecipitation sequencing(ChIP-seq)revealed the binding relationship between KLF13 and HMGCS1.Results:The expression of KLF13 was upregu-lated in HCC tissues and TCGA database.KLF13 knockdown inhibited the proliferation,migration and invasion of HepG2 and Huh7 cells and increased the apoptosis of Huh7 cells.The opposite effects were observed with the overexpression of KLF13 in SK-Hep1 and MHCC-97H cells.The overexpres-sion of KLF13 promoted the growth of HCC in nude mice and KLF13 transcription promoted the expression of HMGCS1 and the biosynthesis of cholesterol.KLF13 knockdown inhibited cholesterol biosynthesis mediated by HMGCS1 and inhibited the growth and metastasis of HCC cells.Conclusions:KLF13 acted as a tumor promoter in HCC by positively regulating HMGCS1-mediated cholesterol biosynthesis.展开更多
文摘为了研究KLF基因家族成员在乳腺癌发生中的分子机制及其与患者预后的关系,我们利用GEPIA对KLF家族进行Kaplan-Meier生存分析,筛选出与患者预后显著相关家族成员;在Oncomine数据库中分析前面筛选出的与乳腺癌预后有关的KLF家族成员;采用c Bio Portal筛选出与患者预后有关的KLF家族成员共表达基因;STRING构建蛋白互作网络,Cytoscape软件中的MCODE插件识别网络模块,再用STRING对网络模块进行聚类分析。Kaplan-Meier生存分析显示KLF家族成员中KLF13和KLF15与乳腺癌预后显著相关（p〈0.05）;Oncomine分析显示只有KLF13在乳腺癌组织表达显著高于正常组织（p〈0.01）;c Bio Portal中筛选出KLF13共表达基因274个;Cytoscape软件中的MCODE插件识别出网络模块3个,STRING进行GO分析发现,网络模块中基因主要参与线粒体内的翻译和呼吸链氧化磷酸化生成ATP等生物过程,KEGG分析发现网络模块中涉及基因主要线粒体蛋白质翻译场所核糖体及其氧化磷酸化等信号通路有关。以上表明KLF13可能通过线粒体信号通路来影响乳腺癌的发生,可作为一个候选的乳腺癌临床预后标志物和潜在的治疗靶点。
基金the Science and Technology Program of Guizhou Province(No.[2019]1267 and[2020]4Y232).
文摘Background and Aims:Krüppel-like factor(KLF)has a role in the occurrence,development and metabolism of can-cer.We aimed to explore the role and potential molecular mechanism of KLF13 in the growth and migration of liver cancer cells.Methods:The expression of KLF13 in hepa-tocellular carcinoma(HCC)tissues was higher than that in normal tissues according to analysis of The Cancer Genome Atlas(TCGA)database.Lentiviral plasmids were used for overexpression and plasmid knockdown of KLF13.Real-time quantitative polymerase chain reaction(qPCR)and western blotting were used to detect mRNA and protein expression in HCC tissues and cells.Cell counting kit-8(CCK-8),colony formation,cell migration and invasion,and flow cytometry assays were used to assess the in vitro function of KLF13 in HCC cells.The effect of KLF13 on xenograft tumor growth in vivo was evaluated.The cholesterol content of HCC cells was determined by an indicator kit.A dual-luciferase reporter assay and chromatin immunoprecipitation sequencing(ChIP-seq)revealed the binding relationship between KLF13 and HMGCS1.Results:The expression of KLF13 was upregu-lated in HCC tissues and TCGA database.KLF13 knockdown inhibited the proliferation,migration and invasion of HepG2 and Huh7 cells and increased the apoptosis of Huh7 cells.The opposite effects were observed with the overexpression of KLF13 in SK-Hep1 and MHCC-97H cells.The overexpres-sion of KLF13 promoted the growth of HCC in nude mice and KLF13 transcription promoted the expression of HMGCS1 and the biosynthesis of cholesterol.KLF13 knockdown inhibited cholesterol biosynthesis mediated by HMGCS1 and inhibited the growth and metastasis of HCC cells.Conclusions:KLF13 acted as a tumor promoter in HCC by positively regulating HMGCS1-mediated cholesterol biosynthesis.
