【摘要】 目的 lncRNAs在不同种族肝细胞癌中的表达异同目前并不明确。文中旨在分析TCGA数据库中黄色人种、白色人种和黑色人种肝细胞癌共有和特有lncRNAs差异谱并预测其功能和调控机制。方法通过对黄色人种、白色人种和黑色人种的HCC患者的癌和癌旁组织进行差异分析得到各自的差异的lncRNAs,并比较3个人种差异lncRNAs基因谱情况,用韦恩图找出3个人种共有的差异lncRNAs。并对筛选出的差异lncRNAs进行生存分析、ceRNA网络构建和靶基因预测并对靶基因行GO、KEGG富集分析和转录因子预测,从而预测其调控机制。结果 3个人种共有的肝细胞癌差异lncRNAs 49个,白色人种和黑色人种重叠基因21.5%,白色人种与黄色人种、黑色人种与黄色人种差异lncRNAs重叠率仅为7.8%和5.8%。3个人种共有的LINC01224可预测到靶基因,行GO富集分析显示,其功能和DNA复制、转位、基因表达调控、表观遗传、miRNAs基因沉默及RNA转录后基因沉默等有关;KEGG分析显示,LINC01224和细胞周期调控、DNA复制相关。白色人种生存相关的的11个lncRNAs基因中未预测到靶基因。黄色人种肝细胞癌生存相关的6个lncRNAs中,AC093609.1的靶基因通过GO富集后结果显示,其功能和离子通道活性如钙通道活性、被动跨膜转运蛋白活性有关;KEGG结果显示其参与心肌病、心肌细胞肾上腺素能等信号通路的调控;AC126118.1的靶基因通过GO富集后发现,其靶基因和多种代谢功能相关;KEGG结果也显示其参与脂肪酸降解、ABC转运蛋白、氨基酸代谢等信号通路。结论白色人种和黑色人种lncRNAs表达谱相似性较高,而黄色人种和白色人种、黑色人种差异较大,其中3个人种共有的LINC01224可能参与了调控肿瘤生长;黄色人种特有lncRNA(AC093609.1、AC126118.1)在肿瘤代谢等方面起了重要作用,为后续肝细胞癌的基因验证实验和功能研究奠定了基础。更多还原

【Abstract】 ObjectiveDifferentially-expressed lncRNAs in hepatocellular carcinoma(HCC)among different races remain unclarified at present time. This study aimed to analyze the shared and specific differential expression profiles of lncRNAs in HCC patients of the yellow,white and black races in the TCGA database and predict their functions and regulatory mechanisms.MethodsWe screened differentially expressed lncRNAs in the cancer and paracancer tissues of the HCC patients of the yellow,white and black races,compared differential expression profiles of lncRNAs and identified the common differentially expressed lncRNAs among the three races. We performed COX regression survival analysis on the differentially expressed lncRNAs,constructed a ceRNA network,and predicted the target genes and their regulatory mechanisms by GO and KEGG enrichment analyses and prediction of the transcription factors.ResultsTotally 49 HCC-related lncRNAs were found in all the three races,with 21.5% overlapped in the white and black races,7.8% in the white and yellow and 5.8% in the black and Asians. GO enrichment analysis showed that the target genes of LINC01224 in the all three races were related to DNA replication and transposition,gene expression regulation,epigenetics,silencing of miRNAs,and gene silencing after RNA transcription,while KEGG analysis revealed a correlation of LINC01224 with the cell cycle and DNA replication. Target genes were not predicted in the 11 survival-related lncRNAs in the patients of the white race. Of the6 survival-related lncRNAs in the yellow patients,the target gene of AC093609.1 was shown to be involved in the activity of the ionic channel,regulation of cardiomyopathy-and cardiomyocyte adrenalin-related signaling pathways,various metabolic functions,fat degradation,ABC protein transportation,and amino acid metabolism.ConclusionHCC-related expression profiles of lncRNAs have a great similarity between the white and black races,but a high differentiality between the yellow and the white or black. LINC01224 may be involved in the relation of tumor growth in all the three races,while AC093609.1 and AC126118.1 specific of the yellow race play an important role in tumor metabolism.更多还原