Long non-coding RNA expression profiles and related regulatory networks in areca nut chewing-induced tongue squamous cell carcinoma
Long non-coding RNA expression profiles and related regulatory networks in areca nut chewing-induced tongue squamous cell carcinoma
复制标题
槟榔咀嚼诱发的舌鳞状细胞癌中长非编码RNA表达谱及相关调控网络
DOI：
10.3892/ol.2020.12165
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发表时间：
2020-12-01
期刊：
影响因子：
2.9
通讯作者：
Gong, Zhaojian
中科院分区：
文献类型：
--
作者：
Li, Panchun;Zhang, Shanshan;Gong, Zhaojian
咀嚼槟榔是舌鳞状细胞癌（TSCC）发生的一个重要危险因素，尽管其潜在的分子机制尚不清楚。为探讨槟榔咀嚼诱发TSCC的分子机制，本研究采用mRNA和长链非编码（lnc）RNA芯片技术，对5对TSCC及癌旁正常组织进行了全基因组检测。共鉴定出3，860个差异表达基因，包括2，193个lncRNA和1，667个mRNAs。基因组富集分析显示，差异表达的mRNA主要集中在染色体22 q13、8 p21和3 p21区域，并受核因子-κ B（NF-κ B）和干扰素调节因子（IRFs）的调控。独创性通路分析的结果显示，这些mRNA显著富集了炎症免疫相关的信号通路。通过进行加权基因共表达网络分析，构建了mRNA和lncRNA的共表达网络。本研究主要研究NF-κ B、IRF和Th细胞信号通路相关的lncRNA及其mRNA-lncRNA调控网络。据我们所知，本研究是第一个研究槟榔咀嚼诱导的TSCC差异mRNA和lncRNA表达谱。研究发现，在咀嚼槟榔诱导的TSCC中，由IRFs和NF-κ B B驱动的炎症相关mRNA-lncRNA调控网络以及Th细胞相关信号通路发挥重要的致癌作用。这些差异表达的mRNA和lncRNA及其调控网络为进一步分析槟榔咀嚼诱导TSCC的分子机制、候选分子标志物和进一步临床干预的靶点提供了依据。
Areca nut chewing is an important risk factor for developing tongue squamous cell carcinoma (TSCC), although the underlying molecular mechanism is unknown. To determine the potential molecular mechanisms of areca nut chewing-induced TSCC, the present study performed whole-genome detection with five pairs of TSCC and adjacent normal tissues, via mRNA- and long non-coding (lnc)RNA-gene chip analysis. A total of 3,860 differentially expressed genes were identified, including 2,193 lncRNAs and 1,667 mRNAs. Gene set-enrichment analysis revealed that the differentially expressed mRNAs were enriched in chromosome 22q13, 8p21 and 3p21 regions, and were regulated by nuclear factor kappa B (NF-kappa B) and interferon regulatory factors (IRFs). The results of ingenuity pathway analysis revealed that these mRNAs were significantly enriched for inflammatory immune-related signaling pathways. A co-expression network of mRNAs and lncRNAs was constructed by performing weighted gene co-expression network analysis. The present study focused on NF-kappa B-, IRF- and Th cell-signaling pathway-related lncRNAs and the corresponding mRNA-lncRNA regulatory networks. To the best of our knowledge, the present study was the first to investigate differential mRNA- and lncRNA-expression profiles in TSCCs induced by areca nut chewing. Inflammation-related mRNA-lncRNA regulatory networks driven by IRFs and NF-kappa B were identified, as well as the Th cell-related signaling pathways that play important carcinogenic roles in areca nut chewing-induced TSCC. These differentially expressed mRNAs and lncRNAs, and their regulatory networks provide insight for further analysis on the molecular mechanism of areca nut chewing-induced TSCC, candidate molecular markers and targets for further clinical intervention.