CDK6 is upregulated and may be a potential therapeutic target in enzalutamide-resistant castration-resistant prostate cancer
Abstract Background Androgen deprivation therapy (ADT) is still the first-line treatment of prostate cancer (PCa). However, after a certain period of therapy, primary PCa inevitably progresses into castration-resistant PCa (CRPC). Enzalutamide (Enz) is an androgen receptor (AR) signal inhibitor whic...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | European Journal of Medical Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40001-022-00730-y |
| _version_ | 1811328749520551936 |
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| author | Xi Chen Yechen Wu Xinan Wang Chengdang Xu Licheng Wang Jingang Jian Denglong Wu Gang Wu |
| author_facet | Xi Chen Yechen Wu Xinan Wang Chengdang Xu Licheng Wang Jingang Jian Denglong Wu Gang Wu |
| author_sort | Xi Chen |
| collection | DOAJ |
| description | Abstract Background Androgen deprivation therapy (ADT) is still the first-line treatment of prostate cancer (PCa). However, after a certain period of therapy, primary PCa inevitably progresses into castration-resistant PCa (CRPC). Enzalutamide (Enz) is an androgen receptor (AR) signal inhibitor which can delay the progression of CRPC and increase survival of patients with metastatic CRPC. However, the mechanisms involved in enzalutamide-resistant (EnzR) CRPC are still controversial. In the study, we used bioinformatic methods to find potential genes that correlated with the occurrence of EnzR CRPC. Methods We collected RNA sequencing data of the EnzR CRPC cell line LNCaP (EnzR LNCaP) from GSE44905, GSE78201, and GSE150807. We found the hub genes from the three datasets. Then we tested the expression of the hub genes in different databases and the potential drugs that can affect the hub genes. Finally, we verified the hub gene expression and drug function. Results From GSE44905, GSE78201 and GSE150807, we found 45 differentially expressed genes (DEGs) between LNCaP and EnzR LNCaP. Ten hub genes were found in the protein–protein interaction (PPI) network. The expression of hub gene and survival analysis were analyzed by different databases. We found that cyclin-dependent kinase 6 (CDK6) was highly expressed in both the EnzR LNCaP cell and PCa patients. Ten potential small molecules could suppress CDK6 expression as per “CLUE COMMAND” findings. Finally, we found the expression of CDK6 increased in both PCa patients’ samples, CRPC and EnzR PCa cell lines. Three potential CDK6 inhibitors, namely apigenin, chrysin and fisetin, can decrease cell proliferation. Conclusions The study proved that the abnormal overexpression of CDK6 may be a reason behind EnzR CRPC occurrence and suppression CDK6 expression may help treat EnzR CRPC. |
| first_indexed | 2024-04-13T15:31:36Z |
| format | Article |
| id | doaj.art-ee4ac125e8744ced8544453f9fa814a6 |
| institution | Directory Open Access Journal |
| issn | 2047-783X |
| language | English |
| last_indexed | 2024-04-13T15:31:36Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj.art-ee4ac125e8744ced8544453f9fa814a62022-12-22T02:41:23ZengBMCEuropean Journal of Medical Research2047-783X2022-07-0127111310.1186/s40001-022-00730-yCDK6 is upregulated and may be a potential therapeutic target in enzalutamide-resistant castration-resistant prostate cancerXi Chen0Yechen Wu1Xinan Wang2Chengdang Xu3Licheng Wang4Jingang Jian5Denglong Wu6Gang Wu7Department of Urology, Tongji Hospital, School of Medicine，Tongji UniversityDepartment of Urology, Baoshan Branch, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineDepartment of Urology, Tongji Hospital, School of Medicine，Tongji UniversityDepartment of Urology, Tongji Hospital, School of Medicine，Tongji UniversityDepartment of Urology, Tongji Hospital, School of Medicine，Tongji UniversitySuzhou Medical School of Soochow UniversityDepartment of Urology, Tongji Hospital, School of Medicine，Tongji UniversityDepartment of Urology, Tongji Hospital, School of Medicine，Tongji UniversityAbstract Background Androgen deprivation therapy (ADT) is still the first-line treatment of prostate cancer (PCa). However, after a certain period of therapy, primary PCa inevitably progresses into castration-resistant PCa (CRPC). Enzalutamide (Enz) is an androgen receptor (AR) signal inhibitor which can delay the progression of CRPC and increase survival of patients with metastatic CRPC. However, the mechanisms involved in enzalutamide-resistant (EnzR) CRPC are still controversial. In the study, we used bioinformatic methods to find potential genes that correlated with the occurrence of EnzR CRPC. Methods We collected RNA sequencing data of the EnzR CRPC cell line LNCaP (EnzR LNCaP) from GSE44905, GSE78201, and GSE150807. We found the hub genes from the three datasets. Then we tested the expression of the hub genes in different databases and the potential drugs that can affect the hub genes. Finally, we verified the hub gene expression and drug function. Results From GSE44905, GSE78201 and GSE150807, we found 45 differentially expressed genes (DEGs) between LNCaP and EnzR LNCaP. Ten hub genes were found in the protein–protein interaction (PPI) network. The expression of hub gene and survival analysis were analyzed by different databases. We found that cyclin-dependent kinase 6 (CDK6) was highly expressed in both the EnzR LNCaP cell and PCa patients. Ten potential small molecules could suppress CDK6 expression as per “CLUE COMMAND” findings. Finally, we found the expression of CDK6 increased in both PCa patients’ samples, CRPC and EnzR PCa cell lines. Three potential CDK6 inhibitors, namely apigenin, chrysin and fisetin, can decrease cell proliferation. Conclusions The study proved that the abnormal overexpression of CDK6 may be a reason behind EnzR CRPC occurrence and suppression CDK6 expression may help treat EnzR CRPC.https://doi.org/10.1186/s40001-022-00730-yDifferentially expressed genesCastration-resistant prostate cancerEnzalutamideHub geneCyclin-dependent kinase 6Therapeutic target |
| spellingShingle | Xi Chen Yechen Wu Xinan Wang Chengdang Xu Licheng Wang Jingang Jian Denglong Wu Gang Wu CDK6 is upregulated and may be a potential therapeutic target in enzalutamide-resistant castration-resistant prostate cancer European Journal of Medical Research Differentially expressed genes Castration-resistant prostate cancer Enzalutamide Hub gene Cyclin-dependent kinase 6 Therapeutic target |
| title | CDK6 is upregulated and may be a potential therapeutic target in enzalutamide-resistant castration-resistant prostate cancer |
| title_full | CDK6 is upregulated and may be a potential therapeutic target in enzalutamide-resistant castration-resistant prostate cancer |
| title_fullStr | CDK6 is upregulated and may be a potential therapeutic target in enzalutamide-resistant castration-resistant prostate cancer |
| title_full_unstemmed | CDK6 is upregulated and may be a potential therapeutic target in enzalutamide-resistant castration-resistant prostate cancer |
| title_short | CDK6 is upregulated and may be a potential therapeutic target in enzalutamide-resistant castration-resistant prostate cancer |
| title_sort | cdk6 is upregulated and may be a potential therapeutic target in enzalutamide resistant castration resistant prostate cancer |
| topic | Differentially expressed genes Castration-resistant prostate cancer Enzalutamide Hub gene Cyclin-dependent kinase 6 Therapeutic target |
| url | https://doi.org/10.1186/s40001-022-00730-y |
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