Cao Baoping, Song Nanxi, Zhang Meiying, Di Chao, Yang Yang, Lu Youyong, Chen Runsheng, Lu Zhi John, Guo Mingzhou
Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing 100853, China.
These authors contributed equally to this work.
Discov Med. 2016 Mar;21(115):159-71.
Recently, many lncRNAs were found to be deregulated in various human cancers and play important roles in carcinogenesis.
To investigate the association of lncRNAs to gastrointestinal cancers, 12 cases of esophageal cancer and hepatic cancer, 16 cases of gastric cancer and colorectal cancer and their matched adjacent tissue samples, 12 esophageal cancer cell lines, 7 gastric cancer cell lines, 10 colorectal cancer cell lines, and 11 hepatic cancer cell lines were examined. RNA-seq, bioinformatics pipeline, co-expression network, and gene ontology enrichment analysis were performed.
We have identified 23,169 candidate novel lncRNA transcripts. Comparing with protein coding genes the lncRNAs tend to be shorter and have less exons. Remarkably, we found 15 lncRNAs that were down-regulated in all cancer cell lines among all four types of cancers. In addition, we analyzed the differentially expressed lncRNAs in gastrointestinal cancer cells before and after treatment with 5-Aza. Many lncRNAs were up-regulated after 5-Aza treatment, which suggested that the expression of these lncRNAs may be regulated by DNA methylation. Finally, based on the co-expression network and GO enrichment analysis, we predicted that many novel lncRNAs were involved in pathways like apoptosis, cell cycle, cell adhesion, EMT, epigenetic regulation, DNA damage response signaling, and immune response.
Based on RNA-Seq and bioinformatics analysis, we have identified a significant number of novel lncRNAs, which could be involved in important pathways related to gastrointestinal cancer development. Overall, we provide a rich resource for identifying new biomarkers and studying novel lncRNA regulation pathways in gastrointestinal cancer.
最近，许多长链非编码RNA（lncRNA）被发现在各种人类癌症中表达失调，并在肿瘤发生中发挥重要作用。
为研究lncRNA与胃肠道癌症的关联，我们检测了12例食管癌和肝癌、16例胃癌和结直肠癌及其匹配的癌旁组织样本、12种食管癌细胞系、7种胃癌细胞系、10种结肠癌细胞系和11种肝癌细胞系。进行了RNA测序、生物信息学分析流程、共表达网络分析和基因本体富集分析。
我们鉴定出23169个候选新型lncRNA转录本。与蛋白质编码基因相比，lncRNA往往较短且外显子较少。值得注意的是，我们发现15种lncRNA在所有四种癌症的所有癌细胞系中均下调。此外，我们分析了5-氮杂胞苷处理前后胃肠道癌细胞中差异表达的lncRNA。5-氮杂胞苷处理后许多lncRNA上调，这表明这些lncRNA的表达可能受DNA甲基化调控。最后，基于共表达网络和基因本体富集分析，我们预测许多新型lncRNA参与了凋亡、细胞周期、细胞黏附、上皮-间质转化、表观遗传调控、DNA损伤应答信号传导和免疫应答等通路。
基于RNA测序和生物信息学分析，我们鉴定出大量新型lncRNA，它们可能参与胃肠道癌症发生发展的重要通路。总体而言，我们为鉴定胃肠道癌症新生物标志物和研究新型lncRNA调控通路提供了丰富资源。
