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- W2949934667 abstract "POH1, a member of the JAMM domain containing deubiquitinases, functions in malignant progression of certain types of cancer. However, the role of POH1 in prostate cancer (PCa) remains unclear.We performed RNA interference against the JAMM members in PC3 cells and analyzed cell proliferation. POH1 knockdown was established to evaluate the effects of POH1 on cell growth in vitro and in vivo. RNA-sequencing was utilized to explore the molecular details underlying the biological function of POH1 in PCa. The expression of POH1 in PCa tissues was detected by immunohistochemistry. The POH1 inhibitor capzimin was evaluated to explore whether pharmacologically inhibiting POH1 significantly affected PCa cell proliferation alone or enhanced the inhibitory efficacy of docetaxel and androgen deprivation.Functional analyses identified POH1 as a JAMM deubiquitinase that is required for PCa proliferation. Importantly, expression of POH1 was higher in human PCa tissues (PCas) than that in normal prostate tissues, and a positive correlation was detected between elevated POH1 expression and higher pathological grades in PCas. In vivo experiments further demonstrated that depleting POH1 significantly suppressed the growth of PCa cell xenografts. POH1 deficiency profoundly inhibited the expression of a set of genes involving the cell cycle and caused G0/G1 phase arrest. Furthermore, the POH1 inhibitor capzimin phenotypically recapitulated the effects of POH1 knockdown and improved the efficacy of docetaxel and androgen deprivation in PCa cells.POH1 was overexpressed in PCas and was correlated with pathological grades in human PCas. Inhibiting POH1 by gene silencing or pharmacological inhibition with capzimin suppressed PCa cell growth. Exploring the inhibition of POH1 in combination with other drugs may provide a strategy to benefit patients with PCa." @default.
- W2949934667 created "2019-06-27" @default.
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- W2949934667 date "2019-06-18" @default.
- W2949934667 modified "2023-09-26" @default.
- W2949934667 title "Targeting POH1 inhibits prostate cancer cell growth and enhances the suppressive efficacy of androgen deprivation and docetaxel" @default.
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- W2949934667 doi "https://doi.org/10.1002/pros.23838" @default.
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