期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
卷 17, 期 1, 页码 188-203出版社
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.50810
关键词
androgen receptor; pre-mRNA processing factor 6; alternative splicing; transcriptional regulation; prostate cancer
资金
- National Natural Science Foundation of China [31871286, 81872015, 31701102, 81702800, 81902889]
- Foundation for Special Professor of Liaoning Province
- Natural Science Foundation of Liaoning Province [20180530072]
PRPF6 plays a key role in enhancing the actions of AR full length and variant 7 in prostate cancer, promoting AR-induced transactivation and tumor growth, as well as being highly expressed in human prostate cancer samples.
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.
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