He Minjie, Lin Yan, Xu Yuzhen
Department of Medical Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650000, P.R. China.
Department of Oncology, The Affiliated Traditional Chinese Medical Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830000, P.R. China.
Oncol Lett. 2019 Mar;17(3):2687-2694. doi: 10.3892/ol.2019.9936. Epub 2019 Jan 15.
Colorectal cancer (CRC) is a highly malignant gastrointestinal tumor accompanied by poor prognosis. Long non-coding RNA (lncRNA) plays an important role in the progression and physiology of tumors as it competes with endogenous RNAs, including miRNA and mRNA. In the present study, a multi-step computational method was used to build a CRC-related functional lncRNA-mediated competitive endogenous RNA (ceRNA) network (LMCN). lncRNAs with more degrees and betweenness centrality (BC) were screened out as hub lncRNAs. Then functional enrichment analyses of lncRNAs were carried out from the Gene Ontology (GO) and Reactome pathway databases based on the 'guilt by association' principle. As a result, lncRNAs in the LMCN displayed specific topological characteristics in accordance with the regulatory correlation of coding mRNAs in CRC pathology. HCP5, EPB41L4A-AS1, SNHG12, and LINC00649 were screened out as hub lncRNAs which were more significantly related to the development and prognosis of CRC. The hub lncRNAs in CRC were obviously involved in functions of cell cycle arrest, vacuolar transport, histone modification, and in pathways of GPCR, signaling by Rho GTPases, axon guidance pathways, meaning that they might be potential biomarkers for diagnosis, evaluation and gene-targeted therapy of CRC. Thus, the LMCN construction method could accelerate lncRNA discovery and therapeutic development in CRC.
结直肠癌（CRC）是一种高度恶性的胃肠道肿瘤，预后较差。长链非编码RNA（lncRNA）在肿瘤的进展和生理过程中发挥着重要作用，因为它与包括miRNA和mRNA在内的内源性RNA相互竞争。在本研究中，采用了一种多步骤计算方法构建了结直肠癌相关的功能性lncRNA介导的竞争性内源性RNA（ceRNA）网络（LMCN）。筛选出具有更多度数和中介中心性（BC）的lncRNA作为枢纽lncRNA。然后基于“关联有罪”原则，从基因本体论（GO）和Reactome通路数据库对lncRNA进行功能富集分析。结果显示，LMCN中的lncRNA根据结直肠癌病理学中编码mRNA的调控相关性呈现出特定的拓扑特征。筛选出HCP5、EPB41L4A-AS1、SNHG12和LINC00649作为与结直肠癌的发生和预后更显著相关的枢纽lncRNA。结直肠癌中的枢纽lncRNA明显参与细胞周期阻滞、液泡运输、组蛋白修饰等功能，以及GPCR、Rho GTPases信号传导、轴突导向通路等途径，这意味着它们可能是结直肠癌诊断、评估和基因靶向治疗的潜在生物标志物。因此，LMCN构建方法可以加速结直肠癌中lncRNA的发现和治疗开发。
