文献类型：期刊文献

英文题名：JARID1D-dependent androgen receptor and JunD signaling activation of osteoclast differentiation inhibits prostate cancer bone metastasis through demethylating H3K4

作者：Hu, Yaohua[1,2];Zhao, Zhite[1,3];Xie, Qinghua[1];Li, Hui[1];Zhang, Chenyang[1,4];He, Xinglin[3];Ma, Yifan[1,4];Zhang, Caiqin[1,2];Li, Qinlong[5,6];Shi, Changhong[1,2]

第一作者：Hu, Yaohua

通信作者：Shi, CH[1];Li, QL[2];Li, QL[3]

机构：[1]Fourth Mil Med Univ, Lab Anim Ctr, Div Canc Biol, Xian 710032, Shaanxi, Peoples R China;[2]State Key Lab Holist Integrat Management Gastroint, Xian 710032, Shaanxi, Peoples R China;[3]Fourth Mil Med Univ, Xijing Hosp, Dept Urol, Xian 710032, Shaanxi, Peoples R China;[4]Gansu Univ Chinese Med, Lanzhou 730030, Peoples R China;[5]Fourth Mil Med Univ, Sch Basic Med, Dept Pathol, Xian, Peoples R China;[6]Fourth Mil Med Univ, Xijing Hosp, State Key Lab Canc Biol, Xian, Peoples R China

第一机构：Fourth Mil Med Univ, Lab Anim Ctr, Div Canc Biol, Xian 710032, Shaanxi, Peoples R China

通信机构：[1]corresponding author), Fourth Mil Med Univ, Lab Anim Ctr, Div Canc Biol, Xian 710032, Shaanxi, Peoples R China;[2]corresponding author), Fourth Mil Med Univ, Sch Basic Med, Dept Pathol, Xian, Peoples R China;[3]corresponding author), Fourth Mil Med Univ, Xijing Hosp, State Key Lab Canc Biol, Xian, Peoples R China.

年份：2025

卷号：15

期号：4

起止页码：1320

外文期刊名：THERANOSTICS

收录：;Scopus(收录号：2-s2.0-85214382759);WOS:【SCI-EXPANDED(收录号:WOS:001414387700008)】；

基金：Funding This work was supported by the National Natural Science Foundation of China (32070532 and 32270566) , Laboratory Animal Foundation Program (No. SYDW_KY 2021-14) , and the Shaanxi Province Innovation Capability Support Plan (2022PT-38) .

语种：英文

外文关键词：JARID1D; demethylase; bone metastasis; prostate cancer; osteoclast differentiation

摘要：Rationale: Bone metastasis and skeletal-related complications are primary causes of mortality in advanced-stage prostate cancer (PCa). Epigenetic regulation, particularly histone modification, plays a key role in this process; however, the underlying mechanisms remain elusive. Methods and Results: In mouse models, JARID1D was an important mediator of both visceral and bone metastases. Chromatin immunoprecipitation (ChIP) and immunofluorescence (IF) techniques showed that the H3K4me3 demethylation activity of JARID1D is a key factor in the dynamic regulation of androgen receptor (AR) expression. Further analysis using western blotting and bone culture systems indicated that knocking down JARID1D enhanced the expression of monoamine oxidase A (MAOA) through the AR signaling pathway, leading to increased secretion of the nuclear factor kappa B (NF-kappa B) ligand receptor activator (RANKL) by PCa cells. This in turn promotes osteoclast differentiation and facilitates bone metastasis. In addition, single-cell sequencing results indicated that a reduction in JARID1D levels directly affected osteoclasts, stimulated JunD transcription, and accelerated PCa bone metastasis progression. Finally, both in vivo and in vitro experiments confirmed that the JARID1D agonist JIB-04 effectively blocked these molecular pathways, thereby delaying the onset of bone metastasis in PCa. Conclusions: These insights provide a theoretical foundation for targeting JARID1D and related molecules in the treatment of PCa bone metastasis.