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

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Abstract

Purpose

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.

Conclusion

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

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Funding

This work was supported by the National Key Research Development Plan (2016YFC0905400), the National Key Basic Research Development Plan (2014CB542006) and the CAMS Innovation Fund for Medical Sciences (2016-I2M-1-001, 2017-I2M-1-005), Beijing Municipal Science & Technology Commission (Z151100004015188).

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Authors and Affiliations

  1. 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

    Jianbing Huang, Yuan Li, Zhiliang Lu, Yun Che, Shouguo Sun, Shuangshuang Mao, Yuanyuan Lei, Ruochuan Zang, Ning Li, Sufei Zheng, Chengming Liu, Xinfeng Wang, Nan Sun & Jie He

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  1. Jianbing Huang
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  2. Yuan Li
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  3. Zhiliang Lu
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  4. Yun Che
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  5. Shouguo Sun
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  6. Shuangshuang Mao
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  7. Yuanyuan Lei
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  8. Ruochuan Zang
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  9. Ning Li
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  11. Chengming Liu
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  12. Xinfeng Wang
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  13. Nan Sun
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  14. Jie He
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Corresponding authors

Correspondence to Nan Sun or Jie He.

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Huang, J., Li, Y., Lu, Z. et al. Analysis of functional hub genes identifies CDC45 as an oncogene in non-small cell lung cancer - a short report. Cell Oncol. 42, 571–578 (2019). https://doi.org/10.1007/s13402-019-00438-y

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