Systematic analysis reveals long noncoding RNAs regulating neighboring transcription factors in human cancers

Abstract

Long noncoding RNAs (lncRNAs) are proposed to play essential roles in regulating gene transcription. Moreover, a subset has been implicated in modulating the expression of the nearby loci. Here we systematically evaluated the relationship between lncRNAs and their neighboring genes based on transcriptome expression profiles from 4900 samples across 12 cancer types. Our findings reveal that lncRNAs, especially those of high syntenic conservation across species, are spatially correlated with transcription factors across the genome. Combining the methods of conservation, co-expression, and causal inference test, we identified a list of 28 lncRNA/TF regulatory pairs across 12 TCGA cancer types, and 19 of which were further confirmed in additional cancer cell lines. Several of these pairs, including PTV1/MYC and GATA6-AS1/GATA6, show prior evidence of regulatory relationships. Other candidates such as LINC00261/FOXA2 and PITRM1-AS1/KLF6 were novel. Our study highlights the significant roles of lncRNAs in tumorigenesis and provides a comprehensive overview of lncRNA regulation on its neighboring TF genes in human cancers.