Although there is an accumulating appreciation of the key roles that long intergenic non-coding RNAs(linc RNAs) play in diverse cellular processes, our knowledge of how linc RNAs 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 linc RNAs.Consistent with previous findings of co-expression between neighboring protein-coding genes, linc RNAs 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 linc RNAs termed "regulatory linc RNAs", representing their dominant roles in gene regulation. The number of regulatory linc RNAs 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 linc RNA,GAS5, affected its predicted protein-coding targets. Moreover, we discovered hundreds of differentially expressed regulatory linc RNAs with inclusion of some cancer-associated linc RNAs. Our integrated analysis reveals enhanced regulatory effects of linc RNAs and provides a resource for the study of regulatory linc RNAs that play critical roles in lung adenocarcinoma.
You ZhouKai WuJianping JiangJinfei HuangPeiwei ZhangYufei ZhuGuohong HuJingyu LangYufang ShiLandian HuTao HuangXiangyin Kong