CDK6 is upregulated and may be a potential therapeutic target in enzalutamide-resistant castration-resistant prostate cancer

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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40001-022-00730-y.