Identification of dysregulated lncRNAs profiling and metastasis-associated lncRNAs in colorectal cancer by genome-wide analysis

摘要

Abstract The colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide, but the pathogenesis of CRC remains not well-known. Increasing studies have highlighted the critical roles of long noncoding RNAs (lncRNAs) in tumorigenesis and cancer cells metastasis, however, the expression pattern, biological roles of lncRNAs, and the mechanisms responsible for their function in CRC remain elusive. In this study, we performed a genome-wide comprehensive analysis of lncRNAs profiling and clinical relevance to identify novel lncRNAs for the further study in CRC. RNA sequencing and microarray data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were annotated and analyzed to find differentially expressed lncRNAs in CRC. Analysis of these datasets revealed that hundreds of lncRNAs expression are dysregulated in CRC tissues when compared with normal tissues. By genomic variation analyses, we identified that some of these lncRNAs dysregulation is associated with the copy number amplification or deletion. Moreover, many lncRNAs expression levels are significantly associated with CRC patients overall and recurrence-free survivals, such as H19, LEF1-AS1, and RP11-296E3.2. Furthermore, we identified one liver metastasis-associated lncRNA termed LUCAT1 in CRC by analyzing lncRNAs expression profiles in the CRC tissues from patients with liver metastasis compared with the CRC tissues without metastasis. Finally, loss-of-function assays determined that knockdown of LUCAT1 could impair CRC cells invasion. Taken together, aberrantly expressed lncRNAs may play critical roles in the development and liver metastasis of CRC, and our findings may provide useful resource for identification of novel biomarkers of CRC.