| Literature DB >> 33854217 |
Donge Tang1,2, Jiaxi He3, Yong Dai2, Xinyan Geng4, Qixin Leng3, Haowu Jiang5, Rui Sun6, Songhui Xu7,8.
Abstract
Post-translational modifications of histones by histone demethylases plays an important role in the regulation of gene transcription and are implicated in cancers. Castrate resistant prostate cancer (CRPC) is often driven by constitutively active androgen receptor and commonly becomes resistant to established hormonal therapy strategies such as enzalutamide as a result. However, the role of KDM1B involved in next generation anti-enzalutamide resistance and the mechanisms of KDM1B regulation are poorly defined. Here, we show that KDM1B is upregulated and correlated with prostate cancer progression and poor prognosis. Downregulation of miR-215 is correlated with overexpression of KDM1B in enzalutamide-resistant prostate cancer cells, which promotes AR-dependent AGR2 transcription and regulates the sensitivity to next generation AR-targeted therapy. Inhibition of KDM1B significantly inhibits prostate tumor growth and improves enzalutamide treatments through AGR2 suppression. Our studies demonstrate inhibition of KDM1B can offer a viable therapeutic option to overcome enzalutamide resistance in tumors with deregulated miR-215-KDM1B-AR-AGR2 signaling axis.Entities:
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Year: 2021 PMID： 33854217 DOI： 10.1038/s41417-021-00332-6
Source DB: PubMed Journal: Cancer Gene Ther ISSN： 0929-1903 Impact factor: 5.987