MYSM1-AR complex-mediated repression of Akt/c-Raf/GSK-3β signaling impedes castration-resistant prostate cancer growth

作者：Jinbo Sun, Xiangnan Hu, Yongheng Gao, Qisheng Tang, Zhining Zhao, Wenjin Xi, Fan Yang, Wei Zhang, Yue Song, Bin Song, Tao Wang, He Wang · 发表于：Aging · 年份：2019 · DOI：10.18632/aging.102482 · 被引用次数：47 · 研究领域：Ubiquitin and proteasome pathways、Prostate Cancer Treatment and Research、Cancer-related Molecular Pathways

. Integrative database analyses and co-immunoprecipitation assays were performed to elucidate genomic association of MYSM1 and MYSM1-involved biological interaction network in PCa. We observed that MYSM1 were downregulated in CRPC compared to localized prostate tumors. Knockdown of MYSM1 promoted cell proliferation and suppressed senescence of CRPC cells under condition of androgen ablation. MYSM1 downregulation enhanced the tumorigenic ability in nude mice. Integrative bioinformatic analyses of the significantly associated genes with MYSM1 revealed MYSM1-correlated pathways, providing substantial clues as to the role of MYSM1 in PCa. MYSM1 was able to bind to androgen receptor instead of increasing its expression and knockdown of MYSM1 resulted in activation of Akt/c-Raf/GSK-3β signaling. Together, our findings indicate that MYSM1 is pivotal in CRPC pathogenesis and may be established as a potential target for future treatment.