Androgen receptor and MYC transcriptomes are equilibrated in multilayer regulatory circuitries in prostate cancer

作者全名："Fu, Bin; Wang, Liyang; Jia, Tianwei; Wei, Zhao; Nama, Nuosu; Liang, Jiaqian; Liao, Xinghua; Liu, XiaMing; Gao, Yanfei; Liu, Xiaoqiang; Mao, Raymond S.; Wang, Keshan; Guo, Ju; Chen, Shaoyong S."

作者地址："[Fu, Bin; Liu, Xiaoqiang; Guo, Ju; Chen, Shaoyong S.] Nanchang Univ, Affiliated Hosp 1, Dept Urol, Nanchang, Peoples R China; [Wang, Liyang; Nama, Nuosu; Chen, Shaoyong S.] Beth Israel Deaconess Med Ctr, Dept Med, Hematol Oncol Div, Boston, MA USA; [Wang, Liyang; Nama, Nuosu; Chen, Shaoyong S.] Harvard Med Sch, , Massachussetts, Boston, MA USA; [Wang, Liyang] Shaanxi Normal Univ, Coll Life Sci, Dept Cell Dev Biol, Xian, Shaanxi, Peoples R China; [Jia, Tianwei] Shandong Univ, Hosp 2, Cheeloo Coll Med, Dept Clin Lab, Jinan, Shandong, Peoples R China; [Jia, Tianwei] Shandong Engn & Technol Res Ctr Tumor Marker Detec, Jinan, Shandong, Peoples R China; [Jia, Tianwei] Shandong Prov Clin Med Res Ctr Clin Lab, Jinan, Shandong, Peoples R China; [Wei, Zhao] Shandong Univ, Qilu Hosp, Dept Clin Lab, Jinan, Shandong, Peoples R China; [Nama, Nuosu] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA; [Liang, Jiaqian] Wuhan 1 Hosp, Dept Urol, Wuhan, Peoples R China; [Liao, Xinghua] Wuhan Univ Sci & Technol, Inst Biol & Med, Coll Life & Hlth Sci, Wuhan, Hubei, Peoples R China; [Liu, XiaMing] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Urol, Wuhan, Hubei, Peoples R China; [Gao, Yanfei] Chongqing Med Univ, Ctr Med Epigenet, Sch Basic Med Sci, Chongqing, Peoples R China; [Mao, Raymond S.; Wang, Keshan] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Urol, Wuhan, Peoples R China; [Wang, Keshan] Huazhong Univ Sci & Technol, Union Hosp, Inst Urol, Tongji Med Coll, Wuhan, Peoples R China; [Wang, Keshan] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Urol, 1277Jiefang Ave, Wuhan 430022, Peoples R China; [Guo, Ju; Chen, Shaoyong S.] Nanchang Univ, Affiliated Hosp 1, Dept Urol, Yongwai St 17, Nanchang 330006, Peoples R China"

通信作者："Wang, KS (通讯作者)，Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Urol, 1277Jiefang Ave, Wuhan 430022, Peoples R China.; Guo, J; Chen, S (通讯作者)，Nanchang Univ, Affiliated Hosp 1, Dept Urol, Yongwai St 17, Nanchang 330006, Peoples R China."

来源：PROSTATE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001045532100001

JCR分区：Q2

影响因子：2.6

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：androgen receptor; dual functions; equilibration; MYC; prostate cancer; transcriptional circuitry

摘要："BackgroundThe discovery of androgen receptor (AR) having transrepression effects completes the circle of its functionalities as a typical transcription factor, which intrinsically bears dual functions of activation and repression linked to co-factor competition and redistribution. Indeed, AR dual functions are exemplified by locus-wide regulation of the oncogenic 8q24-MYC region. MethodsRT-qPCR assay and public RNA-profiling datasets were used to assess MYC transcription in androgen-sensitive cell lines. Public ChIP-seq and RNA-Seq datasets were computed to evaluate AR-MYC direct and indirect signatures. Gene sets in typical MYC and AR pathways were monitored to validate their cross-talks. Bio-informatics and chromosome conformation capture (3C) assay were performed in the AR gene locus to examine androgen-elicited distal regulation. Finally, co-factor re-distribution were globally tracked between AR and MYC binding sites. ResultsIn this report, we found MYC responded negatively to androgen with hypersensitivity, rivaling AR natural functions as an innate androgen effector. Furthermore, both direct and indirect AR and MYC transcriptional programs were actively in equilibration. With established androgen-mediated versus MYC-mediated gene subsets, we validated AR and MYC pathways were both bidirectional and extensively entangled. In addition, we determined that the AR gene locus resembled the MYC gene region and both loci were androgen-repressed via epigenetics and chromatin architectural alterations. Significantly, transcriptional factor profiling along the prostate cancer (PCa) genome exposed that PCa transcriptomes were dynamically equilibrated between AR-binding site and MYC-binding site. ConclusionTogether, our findings stratified AR-MYC interactions that are extensively wired and intricately organized to compensate for essential PCa transcriptional programs and neutralize excessive signaling."

基金机构：General projects of key Ramp;D projects in Jiangxi Province; Foundation of Hubei Province Key Laboratory of Molecular Imaging; Department of Defense; National Institutes of Health [K99/R00]; Natural Science Foundation of Shandong Province; National Natural Science Foundation of China

基金资助正文：General projects of key R & amp;D projects in Jiangxi Province; Foundation of Hubei Province Key Laboratory of Molecular Imaging; Department of Defense grant; National Institutes of Health K99/R00 grant; Natural Science Foundation of Shandong Province; National Natural Science Foundation of China