M6A-related bioinformatics analysis reveals that HNRNPC facilitates progression of OSCC via EMT
M6A-related bioinformatics analysis reveals that HNRNPC facilitates progression of OSCC via EMT
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DOI：
10.18632/aging.103333
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发表时间：
2020-06-30
期刊：
影响因子：
5.2
通讯作者：
Lv, Xiao-Zhi
中科院分区：
文献类型：
--
作者：
Huang, Guang-Zhao;Wu, Qing-Qing;Lv, Xiao-Zhi
越来越多的证据表明，N6-甲基腺苷（m6 A）在癌症进展中起着至关重要的作用。因此，我们的目的是探讨m6 A相关基因在口腔鳞状细胞癌（OSCC）的预后相关性。首先，从癌症基因组图谱（TCGA）下载表达谱，然后提取m6 A相关基因。采用聚类分析和主成分分析（PCA）对m6 A相关基因进行分析。用R软件进行差异表达分析。构建风险模型，筛选关键基因，探讨m6 A基因在口腔鳞癌细胞中的生物学效应。共提取13个m6 A相关基因，并鉴定出8个差异表达基因。随后，基于m6 A的聚类显示了具有不同临床结果的2种亚型。此外，还成功建立了风险模型。在13个m6 A相关基因中，只有异质核核糖核蛋白C（HNRNPC）可能是一个独立的生物标志物，并通过单因素和多因素考克斯回归分析，平均不利的总生存率在口腔鳞癌。功能研究表明，HNRNPC的过表达通过上皮-间充质转化（EMT）促进OSCC的致癌作用。总之，建立了口腔鳞癌中m6 A相关基因的风险模型。随后，HNRNPC被证实促进了OSCC的发生，是OSCC独立的生物标志物和预后标志物，提示其可能成为OSCC新的生物标志物和治疗靶点。
Increasing evidence suggests that N6-methyladenosine (m6A) has a vital role in cancer progression. Therefore, we aimed to explore the prognostic relevance of m6A-related genes in oral squamous cell carcinoma (OSCC). First, Expression profiles were downloaded from The Cancer Genome Atlas (TCGA) and m6A-related genes were extracted afterwards. Then, cluster analysis and principal component analysis (PCA) were used to analyze m6A-related genes. And differentially-expressed analysis was performed in R software. Furthermore, a risk model was constructed, and crucial m6A genes were selected to explore its biological effects in OSCC cells. Total of 13 m6A-related genes were extracted and 8 differentially-expressed genes were identified. Subsequently, m6A-based clustering showed 2 subtypes with different clinical outcome. In addition, a risk model was successfully established. Of 13 m6A-related genes, only heterogeneous nuclear ribonucleoprotein C (HNRNPC) might be an independent biomarker and mean unfavorable overall survival in OSCC by univariate and multivariate cox regression analysis. Functional studies revealed that overexpression of HNRNPC promoted carcinogenesis of OSCC via epithelial- mesenchymal transition (EMT). In total, a risk model of m6A-related genes in OSCC was established. Subsequently, HNRNPC was proved to promote OSCC carcinogenesis and be an independent biomarker prognostic biomarker of OSCC, suggesting that it might be a new biomarker and therapeutic target of OSCC.