目的探讨转录因子叉头框蛋白C1(FOXC1)及FOXC1基因启动子上游转录体(FOXCUT)在乳腺癌组织中的表达及意义。方法 采用Western blot和免疫组化SP法检测65例乳腺癌组织中FOXC1蛋白的表达;采用Real-time PCR法检测FOXC1和FOXCUT mRNA在乳腺...目的探讨转录因子叉头框蛋白C1(FOXC1)及FOXC1基因启动子上游转录体(FOXCUT)在乳腺癌组织中的表达及意义。方法 采用Western blot和免疫组化SP法检测65例乳腺癌组织中FOXC1蛋白的表达;采用Real-time PCR法检测FOXC1和FOXCUT mRNA在乳腺癌组织中的表达,并分析两者mRNA表达的相关性。结果 Western blot和免疫组化染色结果均显示,FOXC1蛋白在乳腺癌组织中的表达显著高于癌旁组织中的表达( P <0.01);Real-time PCR结果显示,与癌旁组织相比,乳腺癌组织中FOXC1 mRNA(5.211±1.555,中位数5.24,95% CI 为4.82~5.59)和FOXCUT mRNA(4.339±0.799,中位数4.17,95% CI 为4.14~4.53)表达量显著上升。相关性分析结果显示,FOXC1与FOXCUT在乳腺癌组织中的表达呈正相关性( r =0.500, P <0.001)。结论 乳腺癌组织中FOXC1和FOXCUT的表达高于癌旁组织,FOXC1与FOXCUT在乳腺癌组织中表达趋势具有相关性,两者可能以基因对形式的发挥功能。展开更多
Background:Triple-negative breast cancer(TNBC)is a type of highly invasive breast cancer with a poor prognosis.According to new research,long noncoding RNAs(lncRNAs)play a significant role in the progression of cancer...Background:Triple-negative breast cancer(TNBC)is a type of highly invasive breast cancer with a poor prognosis.According to new research,long noncoding RNAs(lncRNAs)play a significant role in the progression of cancer.Although the role of lncRNAs in breast cancer has been well reported,few studies have focused on TNBC.This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript(FOXCUT)in triple-negative breast cancer.Methods:Based on a bioinformatic analysis of the cancer genome atlas(TCGA)database,we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues,which was further validated in an external cohort of tissues from the General Surgery Department of the First Affiliated Hospital of Nanjing Medical University.The functions of FOXCUT in proliferation,migration,and invasion were detected in vitro or in vivo.Luciferase assays and RNA immunoprecipitation(RIP)were performed to reveal that FOXCUT acted as a competitive endogenous RNA(ceRNA)for the microRNA miR-24-3p and consequently inhibited the degradation of p38.Results:lncRNA FOXCUT was markedly highly expressed in breast cancer,which was associated with poor prognosis in some cases.Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo.Mechanistically,FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38,which might act as an oncogene in breast cancer.Conclusion:Collectively,this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.展开更多
文摘目的探讨转录因子叉头框蛋白C1(FOXC1)及FOXC1基因启动子上游转录体(FOXCUT)在乳腺癌组织中的表达及意义。方法 采用Western blot和免疫组化SP法检测65例乳腺癌组织中FOXC1蛋白的表达;采用Real-time PCR法检测FOXC1和FOXCUT mRNA在乳腺癌组织中的表达,并分析两者mRNA表达的相关性。结果 Western blot和免疫组化染色结果均显示,FOXC1蛋白在乳腺癌组织中的表达显著高于癌旁组织中的表达( P <0.01);Real-time PCR结果显示,与癌旁组织相比,乳腺癌组织中FOXC1 mRNA(5.211±1.555,中位数5.24,95% CI 为4.82~5.59)和FOXCUT mRNA(4.339±0.799,中位数4.17,95% CI 为4.14~4.53)表达量显著上升。相关性分析结果显示,FOXC1与FOXCUT在乳腺癌组织中的表达呈正相关性( r =0.500, P <0.001)。结论 乳腺癌组织中FOXC1和FOXCUT的表达高于癌旁组织,FOXC1与FOXCUT在乳腺癌组织中表达趋势具有相关性,两者可能以基因对形式的发挥功能。
基金funded by the National Natural Science Foundation of China(Nos.82072931 and 82002805)
文摘Background:Triple-negative breast cancer(TNBC)is a type of highly invasive breast cancer with a poor prognosis.According to new research,long noncoding RNAs(lncRNAs)play a significant role in the progression of cancer.Although the role of lncRNAs in breast cancer has been well reported,few studies have focused on TNBC.This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript(FOXCUT)in triple-negative breast cancer.Methods:Based on a bioinformatic analysis of the cancer genome atlas(TCGA)database,we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues,which was further validated in an external cohort of tissues from the General Surgery Department of the First Affiliated Hospital of Nanjing Medical University.The functions of FOXCUT in proliferation,migration,and invasion were detected in vitro or in vivo.Luciferase assays and RNA immunoprecipitation(RIP)were performed to reveal that FOXCUT acted as a competitive endogenous RNA(ceRNA)for the microRNA miR-24-3p and consequently inhibited the degradation of p38.Results:lncRNA FOXCUT was markedly highly expressed in breast cancer,which was associated with poor prognosis in some cases.Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo.Mechanistically,FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38,which might act as an oncogene in breast cancer.Conclusion:Collectively,this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.
