Liu Yuehui, Ye Fan
Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People's Republic of China.
PeerJ. 2019 Jul 22;7:e7380. doi: 10.7717/peerj.7380. eCollection 2019.
Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumours of the head and neck. Recent evidence has demonstrated that lncRNAs play important roles in tumour progression and could be used as biomarkers for early diagnosis, prognosis, and potential therapeutic targets. The "competitive endogenous RNA (ceRNA)" hypothesis states that lncRNAs competitively bind to miRNAs through their intramolecular miRNA reaction elements (MREs) to construct a wide range of ceRNA regulatory networks. This study aims to predict the role of ceRNA network in LSCC, for advancing the understanding of underlying mechanisms of tumorigenesis.
In this study, the functions of lncRNAs as ceRNAs in LSCC and their prognostic significance were investigated via comprehensive integrated expression profiles data of lncRNAs, mRNAs, and miRNAs obtained from The Cancer Genome Atlas (TCGA). Protein-protein interaction, gene ontology, pathway, and Kaplan-Meier curves analysis were used to profile the expression and function of altered RNAs in LSCC.
As a result, 889 lncRNAs, 55 miRNAs and 1946 mRNAs were found to be differentially expressed in LSCC. These altered mRNAs were mainly involved in extracellular matrix organization, calcium signaling, and metabolic pathways. To study the regulatory function of lncRNAs, an lncRNA-mediated ceRNA network was constructed. This ceRNA network included 61 lncRNAs, seven miRNAs and seven target mRNAs. Of these RNAs, lncRNAs (TSPEAR-AS, CASK-AS1, MIR137HG, PART1, LSAMP-AS1), miRNA (has-mir-210) and mRNAs (HOXC13, STC2, DIO1, FOXD4L1) had a significant effect on the prognosis of LSCC.
The results of this study broaden the understanding of the mechanisms by which lncRNAs are involved in tumorigenesis. Furthermore, five lncRNAs (TSPEAR-AS, CASK-AS1, MIR137HG, PART1, LSAMP-AS1) were identified as potential prognostic biomarkers and therapeutic targets for LSCC. These results provide a basis for further experimental and clinical research.
喉鳞状细胞癌（LSCC）是头颈部最常见的恶性肿瘤之一。最近的证据表明，长链非编码RNA（lncRNA）在肿瘤进展中起重要作用，可作为早期诊断、预后评估的生物标志物以及潜在的治疗靶点。“竞争性内源RNA（ceRNA）”假说指出，lncRNA通过其分子内的微小RNA反应元件（MRE）与微小RNA（miRNA）竞争性结合，从而构建广泛的ceRNA调控网络。本研究旨在预测ceRNA网络在LSCC中的作用，以增进对肿瘤发生潜在机制的理解。
在本研究中，通过从癌症基因组图谱（TCGA）获取的lncRNA、mRNA和miRNA的综合表达谱数据，研究lncRNA作为ceRNA在LSCC中的功能及其预后意义。使用蛋白质-蛋白质相互作用、基因本体论、通路分析以及Kaplan-Meier曲线分析来描述LSCC中差异表达RNA的表达和功能。
结果发现，889个lncRNA、55个miRNA和1946个mRNA在LSCC中差异表达。这些差异表达的mRNA主要参与细胞外基质组织、钙信号传导和代谢途径。为研究lncRNA的调控功能，构建了lncRNA介导的ceRNA网络。该ceRNA网络包括61个lncRNA、7个miRNA和7个靶mRNA。在这些RNA中，lncRNA（TSPEAR-AS、CASK-AS1、MIR137HG、PART1、LSAMP-AS1）、miRNA（has-mir-210）和mRNA（HOXC13、STC2、DIO1、FOXD4L1）对LSCC的预后有显著影响。
本研究结果拓宽了对lncRNA参与肿瘤发生机制的理解。此外，鉴定出5个lncRNA（TSPEAR-AS、CASK-AS1、MIR137HG、PART1、LSAMP-AS1）作为LSCC潜在的预后生物标志物和治疗靶点。这些结果为进一步的实验和临床研究提供了依据。
