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.
Highlights
Colorectal cancer (CRC) is one of the most common malignancies worldwide, and remains the fourth most common malignant cancer in China, with a progressively increasing incidence [1,2,3]
The The Cancer Genome Atlas (TCGA) dataset consists of 480 CRC samples and 41 normal tissue samples, while the GSE41657 dataset consists of 18 paired samples; GSE70880 consists of 20 paired samples; GSE70880 consists of 12 normal mucosae samples and 25 adenocarcinomas samples
Analysis of these datasets showed that 2396 long noncoding RNAs (lncRNAs) expression was dysregulated in the TCGA dataset (793 upregulated and 1603 downregulated); 752 lncRNAs were differentially expressed in the GSE50760 dataset (404 upregulated and 348 downregulated); 220 lncRNAs were dysregulated in the GSE70880 dataset (110 upregulated and 110 downregulated); and 284 lncRNAs were differentially expressed in the GSE41657 dataset (168 upregulated and 116 downregulated) (Fig. 1A– D, and Table S1)
Summary
Colorectal cancer (CRC) is one of the most common malignancies worldwide, and remains the fourth most common malignant cancer in China, with a progressively increasing incidence [1,2,3]. The fast improvement of next- generation sequencing technique and advances in the bioinformatics methods have led to the achievement of human whole genome sequencing and ENCODE (Encyclopedia of DNA Elements) Consortium, which has revealed that only less than 2% of human genome are protein coding genes, while the majority yields thousands of noncoding transcripts [6,7,8]. These transcripts are processed into noncoding RNAs, such as microRNA, pseudogene, and long noncoding RNAs (lncRNAs). Sun et al reported that gastric cancer- associated lncRNA HOXA11-AS promotes cell proliferation and invasion by scaffolding the PRC2, LSD1, and DNMT1, and functioning as competing endogenous RNA for miR- 1297 in gastric cancer [14]
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