新疆汉族食管鳞癌差异表达长链非编码RNA的筛选与分析

Screening and analysis of long non-coding RNA differential expression in Xinjiang Han patients with esophageal squamous cell carcinoma

目的:全基因组关联分析食管癌组织中长链非编码RNA(lncRNA)表达水平的改变及其意义。方法:通过基因芯片技术筛选了6对食管癌及其癌旁正常组织中差异表达的lncRNA和mRNA,通过靶基因预测,利用基因本体论(GO)和Pathway进一步分析lncRNA的功能。结果:差异表达(2倍以上变化且P<0.05)lncRNA共680个,其中161个lncRNA表达上调,519个lncRNA表达下调;差异表达mRNA共1 472个,其中653个mRNA上调,819个mRNA下调。GO和通路分析表明这些差异表达基因参与11条可能与食管鳞癌相关的通路,包括翻译后蛋白修饰调节,粘蛋白O型聚糖的生物合成和鞘糖脂代谢途径等通路,主要涉及分子功能、细胞成分和生物过程的改变。通过顺式和反式调控分析发现共有11个lncRNA有cis-调控的靶基因,1个lncRNA有trans-调控的靶基因,3个lncRNA同时有cis-和trans-调控的靶基因。结论:与癌旁正常组织相比,新疆汉族食管癌组织中lncRNA的表达水平明显改变,差异表达的lncRNA可能通过某些信号通路参与食管癌的发生发展,对进一步寻找食管鳞癌诊断和治疗相关的新的靶点具有重要意义。

Objective To investigate the expression alteration and significance of long non-coding RNA （lncRNA） by GWAS （Genome-wide association study） between Esophageal squamous cell carcinoma （ESCC） and its adjacent normal esophageal tissues. Methods lncRNA and mRNA differential expression in 6 pairs of ESCC and matched non-cancerous tissues were screened by mieroarray assay. The target genes were predicted. Finally, GO （ Gene Ontology ） and Pathway analysis was used for the further research of IneRNA. Results A total of 680 lncRNA and 1472mRNA were differentially expressed at more than two-fold change （P ~〈 0.05, with 1611ncRNA and 653mRNA up-regulated, 5191ncRNA and 819mRNA down-regulated between ESCC and its adjacent normal esophageal tissues. Gene ontology and pathway analysis results suggested that the differentially expressed genes were involved in 11 pathways.Theyare potentially associated with esophageal squamous cell carcinoma, including post-translational protein modification, mucin type O-Glycan biosynthesis and sphingolipid metabolism pathways, which mainly related to the changes of molecular function, cellular components and biological processes. Through cis and trans analysis, a total of 15 differentially expressed lncRNA had cis- and/or trans-regulated target genes in the database, with 13 lncRNA had cis- regulated target genes, 3 lncRNA had trans-regulated target genes, and 1 lncRNA had both cis- and trans-regulated target genes. Conclusion Compared with adjacent normal tissues, a large number of lncRNA were expressed differentially in ESCC in Xinjiang Han people.Aberrantly expressed lncRNA may play important roles in ESCC development and progression through some signaling pathways, which are of great significanee for further search of new targets for the diagnosis and treatment of ESCC.