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PRPF6 促进雄激素受体/雄激素受体变体 7 在去势抵抗性前列腺癌细胞中的作用。

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

机构信息

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.

Department of Breast Surgery, the First Affiliated Hospital of China Medical University, Shenyang City 110001, Liaoning Province, China.

出版信息

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

DOI:10.7150/ijbs.50810
PMID:33390843
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7757026/
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 -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.

摘要

雄激素受体 (AR) 和其变体在前列腺癌的发展和进展中发挥着重要作用。阐明其作用增强的机制对于理解前列腺癌和去势抵抗性前列腺癌转化过程至关重要。在这里，我们提供的证据表明，前体 mRNA 处理因子 6 (PRPF6) 作为 AR 全长 (AR-FL) 和 AR 变体 7 (AR-V7) 作用的关键调节剂，从而参与增强 AR-FL 和 AR-V7 诱导的前列腺癌中的转录激活。此外，PRPF6 被募集到 AR 靶基因的 -调节元件，并与 JMJD1A 结合以增强 AR 诱导的转录激活。PRPF6 还促进 AR-FL 和 AR-V7 的表达。此外，PRPF6 耗竭减少了前列腺癌衍生细胞系中的肿瘤生长，并在小鼠模型中即使在去势条件下也显著抑制异种移植肿瘤。此外，PRPF6 在人前列腺癌样本中明显高表达。总之，我们的研究结果表明 PRPF6 参与增强致癌性 AR 信号，这支持了 PRPF6 在前列腺癌和去势抵抗性前列腺癌进展过程中的一个以前未知的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91cd/7757026/158940b7b3d8/ijbsv17p0188g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91cd/7757026/5fdc112dc878/ijbsv17p0188g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91cd/7757026/c66d3b469b53/ijbsv17p0188g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91cd/7757026/ea9dcf57eca1/ijbsv17p0188g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91cd/7757026/fa79cdc71c4d/ijbsv17p0188g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91cd/7757026/789d8517c518/ijbsv17p0188g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91cd/7757026/7b03f1616e74/ijbsv17p0188g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91cd/7757026/158940b7b3d8/ijbsv17p0188g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91cd/7757026/5fdc112dc878/ijbsv17p0188g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91cd/7757026/c66d3b469b53/ijbsv17p0188g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91cd/7757026/ea9dcf57eca1/ijbsv17p0188g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91cd/7757026/fa79cdc71c4d/ijbsv17p0188g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91cd/7757026/789d8517c518/ijbsv17p0188g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91cd/7757026/7b03f1616e74/ijbsv17p0188g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91cd/7757026/158940b7b3d8/ijbsv17p0188g007.jpg

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