Tian Yan, Xu Yu, Wang Huawei, Shu Ruo, Sun Liang, Zeng Yujian, Gong Fangyou, Lei Yi, Wang Kunhua, Luo Huayou
Department of Gastrointestinal and Hernia Surgery, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Kunming, 650032, China.
Yunnan Institute of Digestive Disease, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Kunming, 650032, China.
Funct Integr Genomics. 2019 Mar;19(2):311-327. doi: 10.1007/s10142-018-0641-9. Epub 2018 Nov 16.
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.
越来越多的数据表明，环状RNA（circRNAs）和长链非编码RNA（lncRNAs）在肿瘤发生中发挥着重要作用。然而，它们在结直肠癌（CRC）中的作用机制仍不清楚。在此，我们鉴定出了数百种显著表达的circRNAs、数千种lncRNAs以及mRNAs。通过qRT-PCR，分别在24对组织和血液样本中验证了一种异常的circRNA、lncRNA和三种mRNA。然后，通过基因本体（GO）分析，我们发现人类CRC组织中上调的circRNAs的线性对应物的基因表达谱倾向于GTPase活性的正调控、细胞蛋白质代谢过程和蛋白质结合，而CRC中下调的circRNAs的基因表达谱则倾向于细胞代谢过程、乙酰辅酶A代谢过程和蛋白激酶C活性的正调控。此外，京都基因与基因组百科全书（KEGG）通路分析表明，p53信号通路是上调的蛋白质编码基因中的重要通路，而环磷酸鸟苷-蛋白激酶G（cGMP-PKG）信号通路是下调转录本中富集程度最高的KEGG通路。此外，lncRNA-mRNA共表达分析表明，下调的lncRNA uc001tma.3与细胞分裂周期蛋白45（CDC45）呈负相关，与超长链脂肪酸延伸酶4（ELOVL4）、血管内皮钙黏蛋白（BVES）、细丝蛋白A（FLNA）和热休克蛋白β8（HSPB8）呈正相关，而上调的lncRNA NR_110882与卷曲蛋白2（FZD2）呈正相关。此外，lncRNA-转录因子（TF）共表达分析表明，最相关的TFs是叉头框蛋白A1（FOXA1）、转录起始因子IID亚基7（TAF7）和腺病毒早期区域1A（E1A）相关蛋白p300（EP300）。我们的研究结果为circRNAs和lncRNAs提供了新的视角，并为进一步研究circRNAs和lncRNAs在结直肠癌中的潜在作用奠定了基础。
