LncRNA-p21 alters the antiandrogen enzalutamide-induced prostate cancer neuroendocrine differentiation via modulating the EZH2/STAT3 signaling

dc.contributor.authorLuo, Jie
dc.contributor.authorWang, Keliang
dc.contributor.authorYeh, Shuyuan
dc.contributor.authorSun, Yin
dc.contributor.authorLiang, Liang
dc.contributor.authorXiao, Yao
dc.contributor.authorXu, Wanhai
dc.contributor.authorNiu, Yuanjie
dc.contributor.authorCheng, Liang
dc.contributor.authorMaity, Sankar N.
dc.contributor.authorJiang, Runze
dc.contributor.authorChang, Chawnshang
dc.contributor.departmentPathology and Laboratory Medicine, School of Medicineen_US
dc.date.accessioned2019-08-26T18:54:19Z
dc.date.available2019-08-26T18:54:19Z
dc.date.issued2019-06-12
dc.description.abstractWhile the antiandrogen enzalutamide (Enz) extends the castration resistant prostate cancer (CRPC) patients' survival an extra 4.8 months, it might also result in some adverse effects via inducing the neuroendocrine differentiation (NED). Here we found that lncRNA-p21 is highly expressed in the NEPC patients derived xenograft tissues (NEPC-PDX). Results from cell lines and human clinical sample surveys also revealed that lncRNA-p21 expression is up-regulated in NEPC and Enz treatment could increase the lncRNA-p21 to induce the NED. Mechanism dissection revealed that Enz could promote the lncRNA-p21 transcription via altering the androgen receptor (AR) binding to different androgen-response-elements, which switch the EZH2 function from histone-methyltransferase to non-histone methyltransferase, consequently methylating the STAT3 to promote the NED. Preclinical studies using the PDX mouse model proved that EZH2 inhibitor could block the Enz-induced NED. Together, these results suggest targeting the Enz/AR/lncRNA-p21/EZH2/STAT3 signaling may help urologists to develop a treatment for better suppression of the human CRPC progression.en_US
dc.identifier.citationLuo, J., Wang, K., Yeh, S., Sun, Y., Liang, L., Xiao, Y., … Chang, C. (2019). LncRNA-p21 alters the antiandrogen enzalutamide-induced prostate cancer neuroendocrine differentiation via modulating the EZH2/STAT3 signaling. Nature communications, 10(1), 2571. doi:10.1038/s41467-019-09784-9en_US
dc.identifier.urihttps://hdl.handle.net/1805/20585
dc.language.isoen_USen_US
dc.publisherSpringer Natureen_US
dc.relation.isversionof10.1038/s41467-019-09784-9en_US
dc.relation.journalNature Communicationsen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/3.0/us*
dc.sourcePMCen_US
dc.subjectUrological canceren_US
dc.subjectProstate canceren_US
dc.titleLncRNA-p21 alters the antiandrogen enzalutamide-induced prostate cancer neuroendocrine differentiation via modulating the EZH2/STAT3 signalingen_US
dc.typeArticleen_US
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