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DHX15 is up‐regulated in castration‐resistant prostate cancer and required for androgen receptor sensitivity to low DHT concentrations
Author(s) -
Xu Yadong,
Song Qiong,
Pascal Laura E.,
Zhong Mingming,
Zhou Yibin,
Zhou Jianhua,
Deng FangMing,
Huang Jiaoti,
Wang Zhou
Publication year - 2019
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23773
Subject(s) - enzalutamide , prostate cancer , androgen receptor , gene knockdown , cancer research , small interfering rna , immunostaining , downregulation and upregulation , coactivator , cancer , prostate , androgen , medicine , tissue microarray , androgen deprivation therapy , biology , transfection , immunohistochemistry , cell culture , hormone , gene , biochemistry , transcription factor , genetics
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‐immunoprecipitation assay. Results The expression level of DHX15 was upregulated in human CRPC specimens compared with hormone naïve 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.