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- W4280491643 abstract "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 (MDV3100) 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. Methods We collected RNA-seq 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 the Cancer Genome Atlas (TCGA) database and the potential drugs that affect the hub genes. Finally, we verified the hub gene expression and drug function. Results From GSE44905, GSE78201 and GSE150807, we found 45 differently expressed genes (DEGs) between LNCaP and EnzR LNCaP. Ten hub genes were found in the protein-protein interaction (PPI) network. The hub genes expression and survival analysis were analyzed by GEPIA depend on the TCGA database. 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 CMap findings. Finally, we found the expression of CDK6 increased in both PCa patients’ samples, CRPC cell lines and EnzR PCa cell lines. Three potential CDK6 inhibitors, namely apigenin, chrysin and fisetin, can decrease cell proliferation. Conclusions The study proved that CDK6 mutation may be a reason behind EnzR CRPC occurrence and suppression CDK6 expression may help treat EnzR CRPC." @default.
- W4280491643 created "2022-05-22" @default.
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- W4280491643 date "2022-05-12" @default.
- W4280491643 modified "2023-10-15" @default.
- W4280491643 title "CDK6 is upregulated and may be a potential therapeutic target in enzalutamide-resistant castration- resistant prostate cancer by bioinformatic analysis" @default.
- W4280491643 doi "https://doi.org/10.21203/rs.3.rs-1501682/v2" @default.
- W4280491643 hasPublicationYear "2022" @default.
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