Role of DNA methylation regulation of miR-130b expression in human lung cancer using bioinformatics analysis
Role of DNA methylation regulation of miR-130b expression in human lung cancer using bioinformatics analysis
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使用生物信息学分析 DNA 甲基化调控 miR-130b 表达在人肺癌中的作用
DOI：
10.1080/15287394.2019.1667634
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发表时间：
2019-09
期刊：
影响因子：
--
通讯作者：
Li Jianxiang
中科院分区：
文献类型：
--
作者：
Wang Jin;Yu Xiao Fan;OUYang Nan;Luo Qiulin;Tong Jian;Chen Tao;Li Jianxiang
MicroRNAs （miRNAs）参与多种关键的生物学过程，包括细胞分化、增殖和迁移的调控，并与肿瘤的发展密切相关。本研究旨在探讨miR-130b在肺癌患者组织中的表达水平。检索两个GEO （Gene Expression Omnibus）数据库GSE48414和GSE74190，以及两个TCGA （The Cancer Genome Atlas）数据库TCGA LUAD和TCGA LUSC，获取差异表达分析和临床病理相关性分析信息。结果显示，miR-130b在肺癌组织中的表达水平明显高于正常组织。数据还表明，肿瘤临床分期、肿瘤侵袭深度等混杂因素显著影响肿瘤患者miR-130b的表达水平。通过4个在线靶基因预测网站，共鉴定出169个miR-130b表达修饰的靶基因。进一步的富集分析表明，这169个靶基因在几个癌症相关的生物学过程和信号通路中显著富集，包括伤口愈合、细胞增殖、Wnt信号、Ras信号和mTOR信号。研究肺癌患者miR-130b编码基因启动子区域的7个位点，然后将这些位点的甲基化与miR-130b表达进行比较，也是一项有趣的研究。TCGA数据集中编码基因甲基化与miR-130b表达的相关性分析显示，启动子区域甲基化降低与miR-130b表达升高显著相关。这种现象明显依赖于吸烟史和临床病理特征。综上所述，数据显示miR-130b编码基因DNA启动子区甲基化的改变与肺癌患者miR-130b表达紊乱相关，提示DNA甲基化过程和miR-130b表达可能作为肺癌检测的生物标志物。
ABSTRACT MicroRNAs (miRNAs) are involved in various crucial biological processes including regulation of cell differentiation, proliferation, and migration, and are closely associated with tumor development. This study aimed to investigate miR-130b expression levels in lung cancer patient tissues. Two Gene Expression Omnibus (GEO) databases, including GSE48414 and GSE74190, and two The Cancer Genome Atlas (TCGA) databases including TCGA LUAD and TCGA LUSC, were accessed to obtain information for differential expression analysis and clinical-pathological correlation analysis. The results showed that miR-130b expression levels were significantly increased in lung cancer compared to normal tissues. Data also demonstrated that confounding factors such as tumor clinical stages and tumor invasion depth markedly affected miR-130b expression levels in cancer patients. A total of 169 target genes modified by miR-130b expression were identified by using 4 online websites for target gene prediction. Further enrichment analysis indicated that these 169 target genes were significantly enriched in several cancer-related biological processes and signaling pathways, including wound healing, cell proliferation, Wnt signaling, Ras signaling, and mTOR signaling. It was also of interest to examine the seven sites on the promoter region of miR-130b encoding gene in lung cancer patients and then compare methylation at these loci with miR-130b expression. The correlation analysis between encoding gene methylation and miR-130b expression in TCGA datasets revealed that decreased methylation in the promoter region was significantly associated with elevated miR-130b expression. This phenomenon was markedly dependent upon smoking history and clinical-pathological features. In conclusion, data indicated alterations in the methylation of DNA promoter region of miR-130b encoding gene were associated with disturbances in miR-130b expression in lung cancer patients suggesting that the DNA methylation process and miR-130b expression may serve as biomarkers for detection of lung cancer.
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