目的探究长链非编码RNA(lncRNA)HAGLR在乳腺癌中的表达情况及其对乳腺癌预后的影响,并构建竞争性内源RNA(ceRNA)网络。方法采用Atlas of Genetics and Cytogenetics in Oncology and Haematology网站检索HAGLR基因染色体定位及转录本表...目的探究长链非编码RNA(lncRNA)HAGLR在乳腺癌中的表达情况及其对乳腺癌预后的影响,并构建竞争性内源RNA(ceRNA)网络。方法采用Atlas of Genetics and Cytogenetics in Oncology and Haematology网站检索HAGLR基因染色体定位及转录本表达情况。采用lnclocater网站预测HAGLR亚细胞定位。通过lnCAR数据库分析HAGLR在乳腺癌组织和癌旁组织的差异表达情况,按HAGLR表达水平,将lnCAR数据库患者分为HAGLR高表达组和HAGLR低表达组,采用Kaplan-Meier法分析两组间总生存(OS)及无转移生存情况,并通过UCSC Xena数据库进行验证。通过lnCAR数据库检索HAGLR共表达基因,将排位前200个共表达基因提交至Metascape网站,进行基因本体(GO)、京都基因和基因组百科全书(KEGG)功能富集分析,构建蛋白互作网络(PPI)。采用生物信息学在线分析网站starbase预测HAGLR靶向的微RNA(miRNA)和可直接编码蛋白的mRNA,通过Cytoscape3.8软件构建HAGLR的ceRNA网络。结果HAGLR基因定位于2q31.1,主要分布于细胞质;HAGLR在乳腺癌组织中的表达水平高于癌旁组织,差异有统计学意义(P<0.001)。对lnCAR数据库和UCSC Xena数据库分析均显示,HAGLR高表达组OS较低表达组均差(均P<0.01);lnCAR数据库中HAGLR高表达组无转移生存较低表达组差(P=0.030)。前200个HAGLR共表达基因中与HAGLR负相关基因129个,与HAGLR正相关基因71个。KEGG通路分析显示,HAGLR与代谢通路、MAPK信号通路、JAK-STAT信号通路及癌症通路有关;GO注释分析显示,HAGLR主要富集在细胞周期、着丝粒复合体组装、有丝分裂进程、蛋白激酶结合、激酶活性的调节、细胞对DNA损伤刺激的反应等多种功能中。hsa-miR-130b-3p、hsa-miR-1245b-5p、hsa-miR-182b-5p、hsa-miR-512-3p、hsa-miR-302b-3p、hsa-miR-185b-5p、hsa-miR-106b-5p为HAGLR靶向miRNA。结论HAGLR在乳腺癌组织中高表达,其可能是乳腺癌预后预测的生物标志物。展开更多
Background:Long non-coding RNAs(lncRNAs)play a vital role in autophagy modulation and tumor progression.However,the key lncRNAs and their functions in gastric cancer(GC)remain largely unknown.Methods:A bioinformatic a...Background:Long non-coding RNAs(lncRNAs)play a vital role in autophagy modulation and tumor progression.However,the key lncRNAs and their functions in gastric cancer(GC)remain largely unknown.Methods:A bioinformatic analysis of GC patients’gene expression profiling data from the Cancer Genome Atlas database was performed to identify autophagy-related lncRNAs that are associated with predictive risk.Through Cox regression and Lasso regression analyses,the autophagy-related lncRNAs that are associated with prognosis were identified,and a novel prognostic model for GC was established.The model was then used to evaluate the clinical features and predictive risk of individuals with GC.By using two datasets,GSE 62254(n=300)and GSE 15459(n=192),from Gene Expression Omnibus,its effectiveness was verified.Gene set enrichment analysis according to hallmark and Kyoto Encyclopedia of Genes and Genomes were used to determine the possible biological roles of these lncRNAs.Furthermore,the HOXD antisense growth-associated long non-coding RNA(HAGLR)mechanism in GC was discovered through in vitro and in vivo experiments.Results:Six lncRNAs associated with autophagy in GC were identified,and a new prognostic risk model based on these lncRNAs was established.The six-lncRNA signature was significantly associated with adverse clinicopathological features and found to be an independent GC prognostic factor.The model was proven to be effective and robust by GSE62254 and GSE15459.According to gene set enrichment analysis,the six lncRNAs appeared to be tightly linked to autophagy-related and cancer-related mechanisms.HAGLR was also found to promote tumor growth by enhancing autophagy signaling in GC.Conclusion:A novel prognostic model integrating HAGLR that can effectively evaluate and predict the prognostic risk of GC patients was established.The results indicated that HAGLR promotes gastric cancer progression by enhancing autophagy and is anticipated to be a potential new target for the treatment of gastric cancer.展开更多
文摘目的探究长链非编码RNA(lncRNA)HAGLR在乳腺癌中的表达情况及其对乳腺癌预后的影响,并构建竞争性内源RNA(ceRNA)网络。方法采用Atlas of Genetics and Cytogenetics in Oncology and Haematology网站检索HAGLR基因染色体定位及转录本表达情况。采用lnclocater网站预测HAGLR亚细胞定位。通过lnCAR数据库分析HAGLR在乳腺癌组织和癌旁组织的差异表达情况,按HAGLR表达水平,将lnCAR数据库患者分为HAGLR高表达组和HAGLR低表达组,采用Kaplan-Meier法分析两组间总生存(OS)及无转移生存情况,并通过UCSC Xena数据库进行验证。通过lnCAR数据库检索HAGLR共表达基因,将排位前200个共表达基因提交至Metascape网站,进行基因本体(GO)、京都基因和基因组百科全书(KEGG)功能富集分析,构建蛋白互作网络(PPI)。采用生物信息学在线分析网站starbase预测HAGLR靶向的微RNA(miRNA)和可直接编码蛋白的mRNA,通过Cytoscape3.8软件构建HAGLR的ceRNA网络。结果HAGLR基因定位于2q31.1,主要分布于细胞质;HAGLR在乳腺癌组织中的表达水平高于癌旁组织,差异有统计学意义(P<0.001)。对lnCAR数据库和UCSC Xena数据库分析均显示,HAGLR高表达组OS较低表达组均差(均P<0.01);lnCAR数据库中HAGLR高表达组无转移生存较低表达组差(P=0.030)。前200个HAGLR共表达基因中与HAGLR负相关基因129个,与HAGLR正相关基因71个。KEGG通路分析显示,HAGLR与代谢通路、MAPK信号通路、JAK-STAT信号通路及癌症通路有关;GO注释分析显示,HAGLR主要富集在细胞周期、着丝粒复合体组装、有丝分裂进程、蛋白激酶结合、激酶活性的调节、细胞对DNA损伤刺激的反应等多种功能中。hsa-miR-130b-3p、hsa-miR-1245b-5p、hsa-miR-182b-5p、hsa-miR-512-3p、hsa-miR-302b-3p、hsa-miR-185b-5p、hsa-miR-106b-5p为HAGLR靶向miRNA。结论HAGLR在乳腺癌组织中高表达,其可能是乳腺癌预后预测的生物标志物。
基金This study was funded by the Natural Science Foundation of Shanghai of China(No.20ZR1452300)National Natural Science Foundation of China(No.81874201)+1 种基金Shanghai Municipal Health Commission Foundation(No.201840359)Natural Science Foundation of Shanghai(No.20ZR1452500).
文摘Background:Long non-coding RNAs(lncRNAs)play a vital role in autophagy modulation and tumor progression.However,the key lncRNAs and their functions in gastric cancer(GC)remain largely unknown.Methods:A bioinformatic analysis of GC patients’gene expression profiling data from the Cancer Genome Atlas database was performed to identify autophagy-related lncRNAs that are associated with predictive risk.Through Cox regression and Lasso regression analyses,the autophagy-related lncRNAs that are associated with prognosis were identified,and a novel prognostic model for GC was established.The model was then used to evaluate the clinical features and predictive risk of individuals with GC.By using two datasets,GSE 62254(n=300)and GSE 15459(n=192),from Gene Expression Omnibus,its effectiveness was verified.Gene set enrichment analysis according to hallmark and Kyoto Encyclopedia of Genes and Genomes were used to determine the possible biological roles of these lncRNAs.Furthermore,the HOXD antisense growth-associated long non-coding RNA(HAGLR)mechanism in GC was discovered through in vitro and in vivo experiments.Results:Six lncRNAs associated with autophagy in GC were identified,and a new prognostic risk model based on these lncRNAs was established.The six-lncRNA signature was significantly associated with adverse clinicopathological features and found to be an independent GC prognostic factor.The model was proven to be effective and robust by GSE62254 and GSE15459.According to gene set enrichment analysis,the six lncRNAs appeared to be tightly linked to autophagy-related and cancer-related mechanisms.HAGLR was also found to promote tumor growth by enhancing autophagy signaling in GC.Conclusion:A novel prognostic model integrating HAGLR that can effectively evaluate and predict the prognostic risk of GC patients was established.The results indicated that HAGLR promotes gastric cancer progression by enhancing autophagy and is anticipated to be a potential new target for the treatment of gastric cancer.
