共表达分析确定miR-92b-3p作为食管鳞状细胞癌中的关键基因发挥作用。
miR-92b-3p Functions As A Key Gene In Esophageal Squamous Cell Cancer As Determined By Co-Expression Analysis.
作者信息
Wang Wanpeng, Fu Sengwang, Lin Xiaolu, Zheng Jinhui, Pu Juan, Gu Yun, Deng Weijun, Liu Yanyan, He Zhongxiang, Liang Wei, Wang Chengshi
机构信息
Department of Radiotherapy, Lianshui County People's Hospital, Kangda College of Nanjing Medical University, Huai'an City, JiangSu, People's Republic of China.
Department of Gastroenterology and Hepatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
出版信息
Onco Targets Ther. 2019 Oct 14;12:8339-8353. doi: 10.2147/OTT.S220823. eCollection 2019.
BACKGROUND
Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy. The aims of the present study were to screen the critical miRNA and corresponding target genes that related to development of ESCC by weighted gene correlation network analysis (WGCNA) and investigate the functions by experimental validation.
METHODS
Datasets of mRNA and miRNA expression data were downloaded from GEO. The R software was used for data preprocessing and differential expression gene analysis. The differentially expressed protein-coding genes (DEGs) and miRNAs (DEMs) were selected (FDR <0.05 or |Fold Change (FC)| >1.5). Meanwhile, 81 expression data of ESCC patients in TCGA combined with clinic information were applied by WGCNA to create networks. The correlational analyses between each module and clinical parameters were conducted, and enrichment analyses of GO and KEGG were subsequently performed. Then, a series of experiments were conducted in ESCC cells by use of miRNA mimics.
RESULTS
In total, 4,023 DEGs and 328 DEMs were screened. After checking good genes and samples, 3,841 genes (3,696 DEGs and 145 DEMs) were used for WGCNA. As a consequence, altogether 11 gene modules were found. Among them, the brown modules were found to be strongly inversely associated with pathological grade. Meanwhile, has-mir-92b, the only miRNA in brown module, had a positive correlation with grade and negatively correlated with potential target gene (KFL4 and DCS2) in the same module. Furthermore, an increased expression of miR-92b-3p and down-regulated KLF4 and DSC2 protein was detected in the ESCC clinical samples. Up-regulated miR-92b-3p shortened G0/G1 phase and promote ESCC cells invasion and migration. Furthermore, we verified that DSC2 and KFL4 was target genes of miR-92b-3p by luciferase report assay.
CONCLUSION
WGCNA is an efficient approach to system biology. By this procedure, miR-92b-3p was identified as an ESCC-promoting gene by target KLF4 and DCS2.
背景
食管鳞状细胞癌（ESCC）是一种侵袭性很强的恶性肿瘤。本研究旨在通过加权基因共表达网络分析（WGCNA）筛选与ESCC发生发展相关的关键miRNA及其相应的靶基因，并通过实验验证来研究其功能。
方法
从基因表达综合数据库（GEO）下载mRNA和miRNA表达数据。使用R软件进行数据预处理和差异表达基因分析。选择差异表达的蛋白质编码基因（DEGs）和miRNA（DEMs）（错误发现率<0.05或|倍数变化（FC）|>1.5）。同时，将TCGA中81例ESCC患者的表达数据与临床信息相结合，通过WGCNA构建网络。对每个模块与临床参数进行相关性分析，随后进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析。然后，在ESCC细胞中使用miRNA模拟物进行一系列实验。
结果
共筛选出4023个DEGs和328个DEMs。在检查了优质基因和样本后，3841个基因（3696个DEGs和145个DEMs）用于WGCNA。结果共发现11个基因模块。其中，棕色模块与病理分级呈显著负相关。同时，棕色模块中唯一的miRNA即hsa - mir - 92b，与分级呈正相关，与同一模块中的潜在靶基因（KLF4和DCS2）呈负相关。此外，在ESCC临床样本中检测到miR - 92b - 3p表达增加，KLF4和DSC2蛋白表达下调。上调miR - 92b - 3p缩短了G0/G1期，促进了ESCC细胞的侵袭和迁移。此外，通过荧光素酶报告基因检测验证了DSC2和KLF4是miR - 92b - 3p的靶基因。
结论
WGCNA是系统生物学的一种有效方法。通过该方法，miR - 92b - 3p通过靶向KLF4和DCS2被鉴定为促进ESCC的基因。
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