机构：[1]Department of Urology, The Second Xiangya Hospital of Central South University, Changsha, China[2]The Third Xiangya Hospital of Central South University, Changsha, China[3]Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania[4]Center for Translational Medicine, Guangxi Medical University, Nanning, China[5]Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China[6]Department of Pathology, NYU School of Medicine, New York, New York[7]Department of Pathology, Duke University School of Medicine, Durham, North Carolina[8]UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania[9]Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Background: DHX15 is a member of the DEAH-box (DHX) RNA helicase family. Our previous study identified it as an AR coactivator which contributes to prostate cancer progression. Methods: We investigated DHX15 expression in castration resistant prostate cancer specimens and the influence of DHX15 on the responsiveness of prostate cancer cells to DHT stimulation. We also explored the role DHX15 played in enzalutamide resistance and the interacting domain in DHX15 with AR. DHX15 expression level in human CRPC specimens and prostate cancer specimens was detected by tissue microarray (TMA) immunostaining analysis. Colony formation assay was performed to determine the proliferation of cells treated with enzalutamide or DHT. siRNAs were used to knockdown DHX15. The interactions between DHX15 and AR were detected using co-im mu noprecipitation assay. Results: The expression level of DHX15 was upregulated in human CRPC specimens compared with hormone naive prostate cancer specimens. DHX15 knockdown reduced AR sensitivity to low DHT concentrations in C4-2 cells. Inactivation of DHX15 sensitizes the enzalutamide treatment in C4-2 cells. Deletion mutagenesis indicated that DHX1 5 interacts with AR through its N terminal domain. Conclusions: These findings suggest that DHX15 contributes to prostate cancer progression. DHX15 is required for androgen receptor sensitivity to low DHT concentrations and contributes to enzalutamide resistance in C4-2 cells. Targeting DHX15 may improve the ADT treatment.
基金：
NIH [R01 CA186780, R50 CA211242]; Department of Defense Prostate Cancer Research Program [W81XWH-14-2-0182, W81XWH-14-20183, W81XWH-14-2-0185, W81XWH-14-2-0186, W81XWH-15-2-0062]
第一作者机构：[1]Department of Urology, The Second Xiangya Hospital of Central South University, Changsha, China[2]The Third Xiangya Hospital of Central South University, Changsha, China[3]Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
通讯作者：
通讯机构：[3]Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania[8]UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania[9]Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
推荐引用方式(GB/T 7714)：
Xu Yadong,Song Qiong,Pascal Laura E.,et al.DHX15 is up-regulated in castration-resistant prostate cancer and required for androgen receptor sensitivity to low DHT concentrations[J].PROSTATE.2019,79(6):657-666.doi:10.1002/pros.23773.
APA：
Xu, Yadong,Song, Qiong,Pascal, Laura E.,Zhong, Mingming,Zhou, Yibin...&Wang, Zhou.(2019).DHX15 is up-regulated in castration-resistant prostate cancer and required for androgen receptor sensitivity to low DHT concentrations.PROSTATE,79,(6)
MLA：
Xu, Yadong,et al."DHX15 is up-regulated in castration-resistant prostate cancer and required for androgen receptor sensitivity to low DHT concentrations".PROSTATE 79..6(2019):657-666
