Department of Gastrointestinal Surgery, Taizhou Municipal Hospital Affiliated with Taizhou University, Taizhou, China.
Department of Clinical Lab Medicine, Taizhou Municipal Hospital Affiliated with Taizhou University, Taizhou, China.
Cancer Med. 2019 Jul;8(8):3875-3891. doi: 10.1002/cam4.2236. Epub 2019 May 22.
Rectal adenocarcinoma (READ) is one of the deadliest malignancies, and the molecular mechanisms underlying the initiation and development of READ remain largely unknown. In this study, we aimed to find key long noncoding RNAs (lncRNAs) and mRNAs in READ by RNA sequencing.
RNA sequencing was performed to identify differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) between READ and normal tissue. READ-specific protein-protein interaction (PPI), DElncRNA-DEmRNA coexpression, and DElncRNA-nearby DEmRNA interaction networks were constructed. DEmRNAs and DEmRNAs coexpressed with DElncRNAs were functionally annotated.
A total of 2113 DEmRNAs and 150 DElncRNAs between READ and normal tissue were identified. The PPI network identified several hub proteins, including CDK1, AURKB, CDC6, FOXQ1, NUF2, and TOP2A. The DElncRNA-DEmRNA coexpression and DElncRNA-nearby DEmRNA interaction networks identified some hub lncRNAs, including CCAT1, LOC105374879, GAS5, and B3GALT5-AS1. The colorectal cancer pathway, the intestinal immune network for IgA production and the p53 signaling pathway were three pathways significantly enriched in DEmRNAs and DEmRNAs coexpressed with DElncRNAs. MSH6 coexpressed with two DElncRNAs (LOC105374879 and CASC15) and BCL2 coexpressed with B3GALT5-AS1 were significantly enriched in the colorectal cancer signaling pathway. TNFRSF17 coexpressed with B3GALT5-AS1 was enriched in the intestinal immune network for IgA production. CCNB2 coexpressed with LOC105374879 was enriched in the p53 signaling pathway.
A total of four DEmRNAs (MSH6, BCL2, TNFRSF17, and CCNB2) and three DElncRNAs (LOC105374879, CASC15, and B3GALT5-AS1) may be involved in the pathogenesis of READ; this data may contribute to understanding the mechanisms of READ and the development of therapeutic strategies for READ.
直肠腺癌(READ)是最致命的恶性肿瘤之一,但其发生和发展的分子机制尚不清楚。本研究旨在通过 RNA 测序寻找 READ 中关键的长链非编码 RNA(lncRNA)和信使 RNA(mRNA)。
通过 RNA 测序鉴定 READ 和正常组织之间差异表达的 mRNA(DEmRNAs)和 lncRNA(DElncRNAs)。构建 READ 特异性蛋白质-蛋白质相互作用(PPI)、DElncRNA-DEmRNA 共表达和 DElncRNA-邻近 DEmRNA 相互作用网络。对 DEmRNAs 和与 DElncRNAs 共表达的 DEmRNAs 进行功能注释。
共鉴定出 2113 个 READ 和正常组织之间的 DEmRNAs 和 150 个 DElncRNAs。PPI 网络鉴定出几个核心蛋白,包括 CDK1、AURKB、CDC6、FOXQ1、NUF2 和 TOP2A。DElncRNA-DEmRNA 共表达和 DElncRNA-邻近 DEmRNA 相互作用网络鉴定出一些核心 lncRNAs,包括 CCAT1、LOC105374879、GAS5 和 B3GALT5-AS1。在 DEmRNAs 和与 DElncRNAs 共表达的 DEmRNAs 中,显著富集了三个通路,即结直肠癌信号通路、肠道免疫网络中 IgA 产生和 p53 信号通路。MSH6 与两个 DElncRNAs(LOC105374879 和 CASC15)共表达,BCL2 与 B3GALT5-AS1 共表达,这两个基因均显著富集在结直肠癌信号通路中。TNFRSF17 与 B3GALT5-AS1 共表达,富集在肠道免疫网络中 IgA 的产生。CCNB2 与 LOC105374879 共表达,富集在 p53 信号通路中。
共鉴定出 4 个 DEmRNAs(MSH6、BCL2、TNFRSF17 和 CCNB2)和 3 个 DElncRNAs(LOC105374879、CASC15 和 B3GALT5-AS1)可能参与 READ 的发病机制;这些数据有助于理解 READ 的发病机制,并为 READ 的治疗策略的发展提供依据。