Int J Biol Sci 2021; 17(1):188-203. doi:10.7150/ijbs.50810

Research Paper

PRPF6 promotes androgen receptor/androgen receptor-variant 7 actions in castration-resistant prostate cancer cells

Wei Liu1, Chunyu Wang1, Shengli Wang1, Kai Zeng1, Shan Wei1, Ning Sun1, Ge Sun1, Manlin Wang1, Renlong Zou1, Wensu Liu1, Lin Lin1, Huijuan Song1, Zining Jin1,3, Yue Zhao1,2✉

1. Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, and Key laboratory of Medical Cell Biology, Ministry of Education, School of Life Sciences, China Medical University, Shenyang City, Liaoning Province110122, China.
2. Department of Molecular Oncology, Liao Ning Tumor Hospital, Shenyang, Liaoning 110042, China.
3. Department of Breast Surgery, the First Affiliated Hospital of China Medical University, Shenyang City 110001, Liaoning Province, China.

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Citation:
Liu W, Wang C, Wang S, Zeng K, Wei S, Sun N, Sun G, Wang M, Zou R, Liu W, Lin L, Song H, Jin Z, Zhao Y. PRPF6 promotes androgen receptor/androgen receptor-variant 7 actions in castration-resistant prostate cancer cells. Int J Biol Sci 2021; 17(1):188-203. doi:10.7150/ijbs.50810. Available from https://www.ijbs.com/v17p0188.htm

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Abstract

Androgen receptor (AR) and its variants play vital roles in development and progression of prostate cancer. To clarify the mechanisms involved in the enhancement of their actions would be crucial for understanding the process in prostate cancer and castration-resistant prostate cancer transformation. Here, we provided the evidence to show that pre-mRNA processing factor 6 (PRPF6) acts as a key regulator for action of both AR full length (AR-FL) and AR variant 7 (AR-V7), thereby participating in the enhancement of AR-FL and AR-V7-induced transactivation in prostate cancer. In addition, PRPF6 is recruited to cis-regulatory elements in AR target genes and associates with JMJD1A to enhance AR-induced transactivation. PRPF6 also promotes expression of AR-FL and AR-V7. Moreover, PRPF6 depletion reduces tumor growth in prostate cancer-derived cell lines and results in significant suppression of xenograft tumors even under castration condition in mouse model. Furthermore, PRPF6 is obviously highly expressed in human prostate cancer samples. Collectively, our results suggest PRPF6 is involved in enhancement of oncogenic AR signaling, which support a previously unknown role of PRPF6 during progression of prostate cancer and castration-resistant prostate cancers.

Keywords: androgen receptor, pre-mRNA processing factor 6, alternative splicing, transcriptional regulation, prostate cancer