Integrative Analysis Reveals Enhanced Regulatory Effects of Human Long Intergenic Non-Coding RNAs in Lung Adenocarcinoma  

作　　者：You Zhou Kai Wu Jianping Jiang Jinfei Huang Peiwei Zhang Yufei Zhu Guohong Hu Jingyu Lang Yufang Shi Landian Hu Tao Huang Xiangyin Kong 

机构地区：[1]State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine [2]State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University

出　　处：《Journal of Genetics and Genomics》2015年第8期423-436,共14页遗传学报（英文版）

基　　金：supported by the National Basic Research Program of China (No. 2011CB510100);the National Natural Science Foundation of China (No. 81030015)

摘　　要：Although there is an accumulating appreciation of the key roles that long intergenic non-coding RNAs （lincRNAs） play in diverse cellular processes, our knowledge of how lincRNAs function in cancer remains sparse. Here, we present a comprehensive landscape of RNA-seq transcriptome profiles of lung adenocarcinomas and their paired normal counterparts to unravel gene regulation rules of lincRNAs. Consistent with previous findings of co-expression between neighboring protein-coding genes, lincRNAs were typically co-expressed with their neighboring genes, which was found in both cancerous and normal tissues. By building a mathematical model based on correlated gene expression, we distinguished an additional subset of lincRNAs termed ＂regulatory lincRNAs＂, representing their dominant roles in gene regulation. The number of regulatory lincRNAs was significantly higher in cancerous compared to normal tissues, and most of them positively regulated protein-coding genes in trans. Functional validation, using knockdown, determined that regulatory lincRNA, GASS, affected its predicted protein-coding targets. Moreover, we discovered hundreds of differentially expressed regulatory lincRNAs with inclusion of some cancer-associated lincRNAs. Our integrated analysis reveals enhanced regulatory effects of lincRNAs and provides a resource for the study of regulatory lincRNAs that play critical roles in lung adenocarcinoma.Although there is an accumulating appreciation of the key roles that long intergenic non-coding RNAs （lincRNAs） play in diverse cellular processes, our knowledge of how lincRNAs function in cancer remains sparse. Here, we present a comprehensive landscape of RNA-seq transcriptome profiles of lung adenocarcinomas and their paired normal counterparts to unravel gene regulation rules of lincRNAs. Consistent with previous findings of co-expression between neighboring protein-coding genes, lincRNAs were typically co-expressed with their neighboring genes, which was found in both cancerous and normal tissues. By building a mathematical model based on correlated gene expression, we distinguished an additional subset of lincRNAs termed ＂regulatory lincRNAs＂, representing their dominant roles in gene regulation. The number of regulatory lincRNAs was significantly higher in cancerous compared to normal tissues, and most of them positively regulated protein-coding genes in trans. Functional validation, using knockdown, determined that regulatory lincRNA, GASS, affected its predicted protein-coding targets. Moreover, we discovered hundreds of differentially expressed regulatory lincRNAs with inclusion of some cancer-associated lincRNAs. Our integrated analysis reveals enhanced regulatory effects of lincRNAs and provides a resource for the study of regulatory lincRNAs that play critical roles in lung adenocarcinoma.

关 键 词：Human long intergenic non-coding RNA Gene regulation Lung adenocarcinoma RNA-seq 

分 类 号：R734.2[医药卫生—肿瘤]