Open AccessSplicing factor PRPF6 upregulates oncogenic androgen receptor signaling pathway in hepatocellular carcinoma
Author(s) -
Song Huijuan,
Sun Ning,
Lin Lin,
Wei Shan,
Zeng Kai,
Liu Wei,
Wang Chunyu,
Zhong Xinping,
Wang Manlin,
Wang Shengli,
Zhou Baosheng,
Lv Chi,
Liu Wensu,
Zhao Yue
Publication year - 2020
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14595
Subject(s) - androgen receptor , cancer research , coactivator , transcription factor , rna splicing , biology , alternative splicing , hepatocellular carcinoma , androgen , signal transduction , splicing factor , endocrinology , medicine , messenger rna , gene , microbiology and biotechnology , cancer , genetics , prostate cancer , rna , hormone
Androgen receptor (AR) signaling is considered to be crucial for the pathogenesis of hepatocellular carcinoma (HCC) with obvious sexual dimorphism. Pre‐mRNA processing factor 6 (PRPF6) was identified as a coactivator of AR. However, the molecular mechanism underlying the modulation function of PRPF6 on AR‐mediated transcriptional activity in HCC needs to be further clarified. In this study, we analyzed data from The Cancer Genome Atlas to show that PRPF6 is highly expressed in HCC. . Our data indicated that PRPF6 interacts with AR/AR splice variants (AR‐Vs) and upregulates AR/AR splice variant 7‐mediated transcriptional activity even without dihydrotestosterone treatment. We observed that AR is obviously induced by androgen treatment and is mainly expressed in the nucleus in HCC‐derived cell lines. Moreover, overexpression of PRPF6 enhances AR expression accompanied with the increase of AR‐Vs expression. We provided evidence that PRPF6 participates in upregulating AR self‐transcription. PRPF6 facilitates the recruitment of AR to the androgen responsive element region of the AR gene. Finally, PRPF6 depletion inhibits cell proliferation in HCC cells and mouse xenografts. Taken together, our results suggest that PRPF6 as a splicing factor enhances AR self‐transcription, thereby coactivating oncogenic AR/AR‐Vs actions in HCC.