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Papers of the Week

2020 Mar 04

Cancer Sci

Targeting the USP1 dependent KDM4A protein stability as a potential prostate cancer therapy.


Cui S-Z, Lei Z-Y, Guan T-P, Fan L-L, Li Y-Q, Geng X-Y, Fu D-X, Jiang H-W, Xu S-H
Cancer Sci. 2020 Mar 04.
PMID: 32133742.


The histone demethylase KDM4A is reported to be overexpressed and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of H3K9 or H3K36 methylation marks. However, the biological role and mechanism of KDM4A in prostate cancer remain unclear. Herein, we reported KDM4A expression was upregulation in PTEN knockout mouse prostate tissue. Depletion of KDM4A in prostate cancer cells inhibited their proliferation and survival in vivo and vitro. Further studies reveal that USP1 is a deubiquitinase that regulates KDM4A K48-linked deubiquitin and stability. Interestingly, we found c-Myc was a key downstream effector of USP1-KDM4A/AR axis in driving prostate cancer cell proliferation. Notably, upregulation of KDM4A expression with high USP1 expression were observed in most prostate tumors and inhibition of USP1 promotes prostate cancer cells response to therapeutic agent_enzalutamide. Our studies propose USP1 may be an anti-cancer therapeutic target in prostate cancer.