Genome-wide analysis of long noncoding RNA signature in human colorectal cancer

Abstract

Long noncoding RNAs (lncRNAs) have been widely regarded as crucial regulators in various biological processes involved in carcinogenesis. However, the comprehensive lncRNA expression signature in colorectal cancer remains fully unknown. We performed a high throughput microarray assay to detect lncRNA expression profile in three paired human colorectal cancer tissues and their adjacent normal tissues. Additional 90 paired colorectal samples were collected to verify differently expression levels of two selected lncRNAs using q-RT-PCR assay. Bioinformatic approaches were performed to explore into the functions of these differently expressed lncRNAs. Microarray assay showed a series of lncRNAs were differently expressed in colorectal cancer. Two of the lncRNAs, HOTAIR and a novel lncRNA, lncRNA-422 were confirmed in more samples (P=0.015 for HOTAIR and P=0.027 for lncRNA-422, respectively). GSEA indicated that gene sets most correlated with them were those named up-regulated in KRAS-over, down-regulated in JAK2-knockout, down-regulated in PDGF-over and down-regulated in TBK1-knockout, all of which were cancer-related. Subsequently, GO analyses of most significantly correlated coding genes of HOTAIR and lncRNA-422 showed that these two lncRNAs may participate in carcinogenesis by regulating protein coding genes involved in special biological process relevant to cancer. Our study demonstrated that different lncRNA expression patterns were involved in colorectal cancer. Besides, HOTAIR and lncRNA-422 were identified to participate in colorectal cancer. Further studies into biological mechanisms of differently expressed lncRNAs identified in our study will help to provide new perspective in colorectal cancer pathogenesis.