Integrative analysis reveals enhanced regulatory effects of human long intergenic non-coding RNAs 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, GAS5, 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.
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, Shanghai 200031, China.
You
Y
Zhou
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, Shanghai 200031, China.
Kai
K
Wu
State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.
Jianping
J
Jiang
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, Shanghai 200031, China.
Jinfei
J
Huang
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, Shanghai 200031, China.
Peiwei
P
Zhang
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, Shanghai 200031, China.
Yufei
Y
Zhu
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, Shanghai 200031, China.
Guohong
G
Hu
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, Shanghai 200031, China.
Jingyu
J
Lang
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, Shanghai 200031, China.
Yufang
Y
Shi
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, Shanghai 200031, China.
Landian
L
Hu
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, Shanghai 200031, China. Electronic address: tohuangtao@126.com.
Tao
T
Huang
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, Shanghai 200031, China. Electronic address: xykong@sibs.ac.cn.
Xiangyin
X
Kong
D000230:Adenocarcinoma / Q000378:metabolism*; D000077192:Adenocarcinoma of Lung; D014408:Biomarkers, Tumor / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008962:Models, Theoretical; D062085:RNA, Long Noncoding / Q000737:chemistry / Q000378:metabolism*; D020537:RNA, Small Nucleolar / Q000378:metabolism; D017423:Sequence Analysis, RNA; D059467:Transcriptome
D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding; D020537:RNA, Small Nucleolar; C109857:growth arrest specific transcript 5
Gene regulation; Human long intergenic non-coding RNA; Lung adenocarcinoma; RNA-seq