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

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

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)423-436
Number of pages14
JournalJournal of Genetics and Genomics
Volume42
Issue number8
DOIs
StatePublished - Aug 20 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics

Keywords

  • Gene regulation
  • Human long intergenic non-coding RNA
  • Lung adenocarcinoma
  • RNA-seq

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