LncRNA PCBP1-AS1-mediated AR/AR-V7 deubiquitination enhances prostate cancer enzalutamide resistance

The refractory of castration-resistant prostate cancer (CRPC) is mainly reflected in drug resistance. The current research on the resistance mechanism of CRPC is still in its infancy. In this study, we revealed for the first time the key role of LncRNA PCBP1-AS1 in CRPC drug resistance. Through deta...

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Veröffentlicht in:	Cell death & disease 2021-09, Vol.12 (10), p.856-11, Article 856
Hauptverfasser:	Zhang, Boya, Zhang, Mingpeng, Shen, Chunyi, Liu, Guancong, Zhang, Fan, Hou, Jingyu, Yao, Weitao
Format:	Artikel
Sprache:	eng
Schlagworte:	13/1 13/105 13/109 13/51 38/47 38/89 45/77 631/337/384/2568 631/67/589/466 631/80/458/582 82/29 Animals Antibodies Benzamides - pharmacology Benzamides - therapeutic use Biochemistry Biomedical and Life Sciences Castration Cell Biology Cell Culture Cell Line, Tumor Cell Movement - genetics Cell Proliferation - genetics Drug resistance Drug Resistance, Neoplasm - genetics Gene Expression Regulation, Neoplastic - drug effects Gene Knockdown Techniques Humans Immunology Life Sciences Male Mice Mice, Nude Models, Biological Nitriles - pharmacology Nitriles - therapeutic use Phenotype Phenylthiohydantoin - pharmacology Phenylthiohydantoin - therapeutic use Prostate cancer Prostatic Neoplasms - drug therapy Prostatic Neoplasms - genetics Prostatic Neoplasms - pathology Prostatic Neoplasms, Castration-Resistant - drug therapy Prostatic Neoplasms, Castration-Resistant - genetics Prostatic Neoplasms, Castration-Resistant - pathology Proteasome Endopeptidase Complex - metabolism Proteasomes Protein Binding Protein Domains Protein Stability Proteolysis Receptors, Androgen - chemistry Receptors, Androgen - metabolism RNA, Long Noncoding - genetics RNA, Long Noncoding - metabolism Tumors Ubiquitin Ubiquitin - metabolism Ubiquitin Thiolesterase - metabolism Ubiquitination - drug effects
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Zusammenfassung:	The refractory of castration-resistant prostate cancer (CRPC) is mainly reflected in drug resistance. The current research on the resistance mechanism of CRPC is still in its infancy. In this study, we revealed for the first time the key role of LncRNA PCBP1-AS1 in CRPC drug resistance. Through detailed in vivo and in vitro studies, we found that PCBP1-AS1 may enhance the deubiquitination of AR/AR-V7 by stabilizing the USP22-AR/AR-V7 complex, thereby preventing AR/AR-V7 from being degraded through the ubiquitin–proteasome pathway. Targeting PCBP1-AS1 can significantly restore the drug sensitivity of enzalutamide-resistant tumors in vivo and in vitro. Our research further expands the function of LncRNA in castration-resistant prostate cancer, which may provide new potential for clinical diagnosis and targeted therapy.
ISSN:	2041-4889 2041-4889
DOI:	10.1038/s41419-021-04144-2