Abstract
Increasing data demonstrate that circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) play important roles in tumorigenesis. However, the mechanisms in colorectal cancer (CRC) remain unclear. Here, hundreds of significantly expressed circRNAs, and thousands of lncRNAs as well as mRNAs were identified. By qRT-PCR, one abnormal circRNA, lncRNA, and three mRNAs were verified in 24 pairs of tissues and blood samples, respectively. Then, by GO analysis, we found that the gene expression profile of linear counterparts of upregulated circRNAs in human CRC tissues preferred positive regulation of GTPase activity, cellular protein metabolic process, and protein binding, while that of downregulated circRNAs of CRC preferred positive regulation of cellular metabolic process, acetyl-CoA metabolic process, and protein kinase C activity. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that p53 signaling pathway was an important pathway in upregulated protein-coding genes, whereas cyclic guanosine monophosphate-protein kinase G (cGMP–PKG) signaling pathway was the top enriched KEGG pathway for downregulated transcripts. Furthermore, lncRNA–mRNA co-expression analysis demonstrated that downregulated lncRNA uc001tma.3 was negatively with CDC45 and positively with ELOVL4, BVES, FLNA, and HSPB8, while upregulated lncRNA NR_110882 was positively with FZD2. In addition, lncRNA–transcription factor (TF) co-expression analysis showed that the most relevant TFs were forkhead box protein A1 (FOXA1), transcription initiation factor TFIID submint 7 (TAF7), and adenovirus early region 1A(E1A)-associated protein p300 (EP300). Our findings offer a fresh view on circRNAs and lncRNAs and provide the foundation for further study on the potential roles of circRNAs and lncRNAs in colorectal cancer.
Highlights
Colorectal cancer (CRC), one of the most common causes of cancer-related deaths in the world, leads to 600,000 deaths each year worldwide (Sostres et al 2014; Ung et al 2014)
Total 1148 long non-coding RNAs (lncRNAs) and 1553 mRNAs between human CRC tissues and adjacent normal tissues were with fold change ≥ 2.0, P < 0.05, and false discovery rate (FDR) < 0.05 (Figs. 2 and 3)
CircRNA, lncRNA, and mRNA expression patterns among samples were different as shown by hierarchical clustering
Summary
Colorectal cancer (CRC), one of the most common causes of cancer-related deaths in the world, leads to 600,000 deaths each year worldwide (Sostres et al 2014; Ung et al 2014). Current detection methods, such as fecal occult blood testing and fiber-optic colonoscopy, have significantly improved outcomes for CRC patients, more than half of those at advanced stage of disease die of cancer recurrence after suffering radical resection (Edwards et al 2014). About 10–20% were the protein-coding RNAs, and the remaining 80–90% were non-protein-coding transcripts, namely non-coding RNAs (Bertone et al 2004; Kapranov et al 2007). Circular RNAs (circRNAs), a widespread form of non-coding RNA in mammalian cells, were formed by non-sequential back-splicing of pre-mRNA transcripts (Conn et al 2015; Memczak et al 2013). In CRC, global reduction circRNA abundance and proliferation revealed a negative correlation (Bachmayr-Heyda et al 2015). The research about the global functional roles of circRNAs in CRC was few reported
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