Identification of CDK2 as a Novel Target in Treatment of Prostate Cancer

Abstract

Aim: This study aims the potential gene involved in the metastasis of prostate cancer (Pca). Methods: PubMed GEO datasets (GSE6605 and GSE6606) were downloaded. We used multiple bioinformatics methods to screen differentially expressed genes in Pca. Gene network was built by STRING and visualized by Cytoscape. All of the hub genes were analyzed by cBioPortal. Inhibition of CDK2 including siRNA, inhibitor and cas9-induced CDK2 knockout was followed by an invasion assay. Downstream genes of CDK2 were analyzed by western blot. Results: Sequencing data were analyzed to screen the genes with expression alterations. The top genes were validated in our samples. 11 hub genes were screened out. Among these genes, STAT3 and CDK2 were significantly associated with recurrence. Further study suggested that inhibition of CDK2 reduced invasion of Pca cell lines. The invasion ability was rescued after reintroduction of CDK2. Conclusion: These data indicated that CDK2 was a crucial factor in metastasis of Pca and might be a novel therapy target.

Keywords::

• cBioPortal
• CDK2
• cell cycle
• GEO database
• hub genes
• metastasis
• overall survival
• PI3K/Akt pathway
• prostate cancer
• recurrence

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/fon-2017-0561

Financial & competing interests disclosure

This work was supported by the National Natural Science Foundation of China (81402100 and 31701298), the Foundation of Health and Family Planning Commission of Jiangsu Province (Q201408), the Social Development Foundation of Zhenjiang (SH2016031 and SH2014026), the Foundation for Young Medical Talents of Jiangsu Province (QNRC2016840), ‘Six Talent Peaks Project’ in Jiangsu Province(WSW-007), the Key Research Foundation of Zhenjiang Social Development (SH2016028) and the Natural Science Foundation of Jiangsu Province (SBK2017040259). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (81402100 and 31701298), the Foundation of Health and Family Planning Commission of Jiangsu Province (Q201408), the Social Development Foundation of Zhenjiang (SH2016031 and SH2014026), the Foundation for Young Medical Talents of Jiangsu Province (QNRC2016840), ‘Six Talent Peaks Project’ in Jiangsu Province(WSW-007), the Key Research Foundation of Zhenjiang Social Development (SH2016028) and the Natural Science Foundation of Jiangsu Province (SBK2017040259). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.