利用生物信息学方法鉴定肺腺癌中与淋巴结转移相关的微小RNA并分析其潜在机制
Identification of lymph node metastasis-related microRNAs in lung adenocarcinoma and analysis of the underlying mechanisms using a bioinformatics approach.
作者信息
Yan Li, Jiao Demin, Hu Huizhen, Wang Jian, Tang Xiali, Chen Jun, Chen Qingyong
机构信息
1 Department of Oncology, The 117th Hospital of PLA, Hangzhou 310013, P.R. China.
2 Department of Respiratory Disease, The 117th Hospital of PLA, Hangzhou 310013, P.R. China.
出版信息
Exp Biol Med (Maywood). 2017 Apr;242(7):709-717. doi: 10.1177/1535370216677353. Epub 2016 Nov 14.
This study aimed to screen lymphatic metastasis-related microRNAs (miRNAs) in lung adenocarcinoma and explore their underlying mechanisms using bioinformatics. The miRNA expression in primary lung adenocarcinoma, matched adjacent non-tumorigenic and lymph node metastasis tissues of patients were profiled via microarray. The screened metastasis-related miRNAs were then validated using quantitative real-time PCR in a second cohort of lung adenocarcinoma patients with lymphatic metastasis. Significance was determined using a paired t-test. Target genes of the metastasis-related miRNAs were predicted using TargetScan, and transcription factors (TFs) were predicted based on the TRANSFAC and ENCODE databases. Furthermore, the related long non-coding RNAs (lncRNAs) were screened with starBase v2.0. The miRNA-TF-mRNA and lncRNA-miRNA-mRNA networks were constructed to determine the key interactions associated with lung adenocarcinoma metastasis. According to the miRNA microarray results, there were 10 miRNAs that were differentially expressed in metastatic tissues compared with primary tumor and adjacent non-tumorigenic tissues. Among them were increased levels of miR-146a-5p, miR-342-3p, and miR-150-5p, which were validated in the second cohort. Based on the miRNA-TF-mRNA network, vascular endothelial growth factor A and transcription factors (TFs) including TP53, SMAD4, and EP300 were recognized as critical targets of the three miRNAs. Interactions involving SNHG16-miR-146a-5p-SMAD4 and RP6-24A23.7-miR-342-3p/miR-150-5p-EP300 were highlighted according to the lncRNA-miRNA-mRNA network. miR-146a-5p, miR-342-3p, and miR-150-5p are lymphatic metastasis-related miRNAs in lung adenocarcinoma. Bioinformatics analyses demonstrated that SNHG16 might inhibit the interaction between miR-146a-5p and SMAD4, while RP6-24A23.7 might weaken miR-342-3p-EP300 and miR-150-5p-EP300 interactions in metastasis.
本研究旨在筛选肺腺癌中与淋巴转移相关的微小RNA（miRNA），并利用生物信息学方法探索其潜在机制。通过微阵列分析患者原发性肺腺癌、配对的相邻非肿瘤组织及淋巴结转移组织中的miRNA表达情况。然后，在另一组发生淋巴转移的肺腺癌患者中，采用定量实时PCR对筛选出的与转移相关的miRNA进行验证。采用配对t检验确定差异的显著性。利用TargetScan预测与转移相关的miRNA的靶基因，并基于TRANSFAC和ENCODE数据库预测转录因子（TF）。此外，用starBase v2.0筛选相关的长链非编码RNA（lncRNA）。构建miRNA-TF-mRNA和lncRNA-miRNA-mRNA网络，以确定与肺腺癌转移相关的关键相互作用。根据miRNA微阵列结果，与原发性肿瘤和相邻非肿瘤组织相比，有10种miRNA在转移组织中差异表达。其中，miR-146a-5p、miR-342-3p和miR-150-5p水平升高，并在另一组中得到验证。基于miRNA-TF-mRNA网络，血管内皮生长因子A和包括TP53、SMAD4和EP300在内的转录因子被确定为这三种miRNA的关键靶点。根据lncRNA-miRNA-mRNA网络，涉及SNHG16-miR-146a-5p-SMAD4和RP6-24A23.7-miR-342-3p/miR-150-5p-EP300的相互作用受到关注。miR-146a-5p、miR-342-3p和miR-150-5p是肺腺癌中与淋巴转移相关的miRNA。生物信息学分析表明，SNHG16可能抑制miR-146a-5p与SMAD4之间的相互作用，而RP6-24A23.7可能在转移过程中削弱miR-342-3p-EP300和miR-150-5p-EP300之间的相互作用。
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