Research Paper Volume 11, Issue 22 pp 10644—10663
MYSM1-AR complex-mediated repression of Akt/c-Raf/GSK-3β signaling impedes castration-resistant prostate cancer growth
- 1 Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, China
- 2 Department of Respiratory and Critical Care Medicine, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, China
- 3 Clinical Laboratory, 451 Hospital of Chinese People's Liberation Army, Xi'an, Shaanxi 710054, China
- 4 State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi’an, Shaanxi 710032, China
- 5 Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi 710032, China
- 6 Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi’an, Shaanxi 710032, China
received: August 20, 2019 ; accepted: November 8, 2019 ; published: November 24, 2019 ;https://doi.org/10.18632/aging.102482
How to Cite
Copyright © 2019 Sun et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Epigenetic alterations that lead to dysregulated gene expression in the progression of castration-resistant prostate cancer (CRPC) remain elusive. Here, we investigated the role of histone deubiquitinase MYSM1 in the pathogenesis of prostate cancer (PCa). Tissues and public datasets of PCa were evaluated for MYSM1 levels. We explored the effects of MYSM1 on cell proliferation, senescence and viability both in vitro and in vivo. 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.