Analysis of functional hub genes identifies CDC45 as an oncogene in non-small cell lung cancer - a short report
Analysis of functional hub genes identifies CDC45 as an oncogene in non-small cell lung cancer - a short report
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DOI：
10.1007/s13402-019-00438-y
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发表时间：
2019-08-01
影响因子：
6.6
通讯作者：
He, Jie
中科院分区：
文献类型：
--
作者：
Huang, Jianbing;Li, Yuan;He, Jie
目的Hub基因是肿瘤靶向治疗的良好分子候选基因。然而，到目前为止，关于HUB基因在非小细胞肺癌(NSCLC)发生中的临床意义和功能特征的信息还很少。本研究旨在分析Hub基因在非小细胞肺癌中的作用。方法利用正常、癌前病变和癌组织的转录数据，采用加权基因共表达网络分析(WGCNA)分析非小细胞肺癌发生发展过程中的基因网络。结果共鉴定出14个与非小细胞肺癌发生发展相关的基因网络，其中绿色和绿色两个模块分别与肿瘤的发生和发展密切相关。基因富集度分析表明，绿松石模块与细胞周期/有丝分裂相关，绿色模块与发育/形态发生相关。我们发现，在肿瘤发生过程中，绿松石模块中HUB基因CDC45、CDCA5、GINS2、RAD51和Troap的表达水平逐渐升高，而绿色模块中MAGI2-AS3和RBMS3基因的表达水平在肿瘤发生过程中逐渐下降。在功能上，我们发现CDC45基因的表达下调抑制了NSCLC细胞在体内外的增殖，并使细胞停滞在细胞周期的G2/M期，支持CDC45的致癌作用。结论通过基因共表达网络分析和后续的功能分析，我们确定了HUB基因CDC45可能是NSCLC的一个新的治疗靶点。
PurposeHub genes are good molecular candidates for targeted cancer therapy. As yet, however, there is little information on the clinical implications and functional characteristics of hub genes in the development of non-small cell lung cancer (NSCLC). In this study, we set out to analyze the role of hub genes in NSCLC.MethodsWe performed weighted gene co-expression network analysis (WGCNA) to analyze gene networks during NSCLC development using transcriptomic data from normal, pre-cancer and cancer tissues. Both in vitro and in vivo expression knockdown assays were used to evaluate the biological function of candidate hub gene CDC45 (cell division cycle 45) in NSCLC.ResultsWe identified 14 gene networks associated with NSCLC development, in which two modules (turquoise and green) correlated with tumorigenesis most positively and negatively, respectively. Gene enrichment analysis showed that the turquoise module was associated with cell cycle/mitosis, and that the green module was associated with development/morphogenesis. We found that the expression levels of the hub genes CDC45, CDCA5, GINS2, RAD51 and TROAP in the turquoise module increased gradually during tumorigenesis, whereas those of MAGI2-AS3 and RBMS3 in the green module decreased during tumorigenesis. Functionally, we found that expression knockdown of CDC45 inhibited NSCLC cell proliferation both in vitro and in vivo, and arrested the cells in the G2/M phase of the cell cycle, supporting an oncogenic role of CDC45.ConclusionThrough gene co-expression network analysis and subsequent functional analyses we identified hub gene CDC45 as a putative novel therapeutic target in NSCLC.