Analysis of functional hub genes identifies CDC45 as an oncogene in non-small cell lung cancer - a short report. 2019

Jianbing Huang, and Yuan Li, and Zhiliang Lu, and Yun Che, and Shouguo Sun, and Shuangshuang Mao, and Yuanyuan Lei, and Ruochuan Zang, and Ning Li, and Sufei Zheng, and Chengming Liu, and Xinfeng Wang, and Nan Sun, and Jie He
Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

OBJECTIVE Hub 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. METHODS We 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. RESULTS We 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. CONCLUSIONS Through gene co-expression network analysis and subsequent functional analyses we identified hub gene CDC45 as a putative novel therapeutic target in NSCLC.

UI MeSH Term Description Entries
D008175 Lung Neoplasms Tumors or cancer of the LUNG. Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008819 Mice, Nude Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses. Athymic Mice,Mice, Athymic,Nude Mice,Mouse, Athymic,Mouse, Nude,Athymic Mouse,Nude Mouse
D002289 Carcinoma, Non-Small-Cell Lung A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy. Carcinoma, Non-Small Cell Lung,Non-Small Cell Lung Cancer,Non-Small Cell Lung Carcinoma,Non-Small-Cell Lung Carcinoma,Nonsmall Cell Lung Cancer,Carcinoma, Non Small Cell Lung,Carcinomas, Non-Small-Cell Lung,Lung Carcinoma, Non-Small-Cell,Lung Carcinomas, Non-Small-Cell,Non Small Cell Lung Carcinoma,Non-Small-Cell Lung Carcinomas
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D052138 Genes, Neoplasm Genes whose abnormal expression, or MUTATION are associated with the development, growth, or progression of NEOPLASMS. Cancer Genes,Neoplasm Genes,Cancer Gene,Gene, Cancer,Gene, Neoplasm,Genes, Cancer,Neoplasm Gene
D053263 Gene Regulatory Networks Interacting DNA-encoded regulatory subsystems in the GENOME that coordinate input from activator and repressor TRANSCRIPTION FACTORS during development, cell differentiation, or in response to environmental cues. The networks function to ultimately specify expression of particular sets of GENES for specific conditions, times, or locations. Gene Circuits,Gene Modules,Gene Networks,Transcriptional Networks,Gene Module,Circuit, Gene,Circuits, Gene,Gene Circuit,Gene Network,Gene Regulatory Network,Module, Gene,Modules, Gene,Network, Gene,Network, Gene Regulatory,Network, Transcriptional,Networks, Gene,Networks, Gene Regulatory,Networks, Transcriptional,Regulatory Network, Gene,Regulatory Networks, Gene,Transcriptional Network

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