Construction and integrated analysis of crosstalking ceRNAs networks in laryngeal squamous cell carcinoma
Construction and integrated analysis of crosstalking ceRNAs networks in laryngeal squamous cell carcinoma
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作者：
Liu, Yuehui;Ye, Fan
背景。喉部鳞状细胞癌是头颈部最常见的恶性肿瘤之一。最近的证据表明，lncrna在肿瘤进展中起着重要作用，可以作为早期诊断、预后和潜在治疗靶点的生物标志物。“竞争性内源性RNA （ceRNA）”假说认为，lncrna通过其分子内miRNA反应元件（MREs）与miRNA竞争性结合，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，以促进对肿瘤发生的潜在机制的理解。材料和方法。本研究通过从癌症基因组图谱（the Cancer Genome Atlas， TCGA）中获得的lncRNAs、mrna和miRNAs的综合表达谱数据，研究lncRNAs作为ceRNAs在LSCC中的功能及其预后意义。通过蛋白-蛋白相互作用、基因本体、通路和Kaplan-Meier曲线分析来分析lscc中改变的rna的表达和功能。结果发现889个lncrna、55个mirna和1946个mrna在LSCC中存在差异表达。这些改变的mrna主要参与细胞外基质组织、钙信号传导和代谢途径。为了研究lncrna的调控功能，我们构建了lncrna介导的ceRNA网络。该ceRNA网络包括61个lncrna、7个mirna和7个靶mrna。其中lncRNAs （tspeara - 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。这项研究的结果拓宽了对lncrna参与肿瘤发生机制的理解。此外，5个lncrna （TSPEARAS、CASK-AS1、MIR137HG、PART1、LSAMP-AS1）被确定为LSCC的潜在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。
Background. 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.Material and Methods. 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.Results. 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.Conclusion. The results of this study broaden the understanding of the mechanisms by which lncRNAs are involved in tumorigenesis. Furthermore, five lncRNAs (TSPEARAS, 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.