Ruan Lin, Wang Lei, Wang Xiaosong, He Ming, Yao Xiaoguang
Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, China.
Department of Nephrology, The First Hospital of Hebei Medical University, Shijiazhuang, China.
Oncotarget. 2017 Dec 11;9(2):2002-2016. doi: 10.18632/oncotarget.23111. eCollection 2018 Jan 5.
The epigenetic factor SIRT1 can promote prostate cancer progression, but it is unclear whether SIRT1 contributes to neuroendocrine differentiation. In this study, we showed that androgen deprivation can induce reactive oxygen species production and that reactive oxygen species, in turn, activate SIRT1 expression. The increased SIRT1 expression induces neuroendocrine differentiation of prostate cancer cells by activating the Akt pathway. In addition, the interaction between Akt and SIRT1 is independent of N-Myc and can drive the development of neuroendocrine prostate cancer when N-Myc is blocked. Furthermore, SIRT1 facilitates tumor maintenance, and targeting SIRT1 may reduce the tumor burden during androgen deprivation. Our findings suggest that SIRT1 is a potential target for therapeutic intervention.
表观遗传因子SIRT1可促进前列腺癌进展，但尚不清楚SIRT1是否参与神经内分泌分化。在本研究中，我们发现雄激素剥夺可诱导活性氧生成，而活性氧反过来又会激活SIRT1表达。SIRT1表达增加通过激活Akt途径诱导前列腺癌细胞的神经内分泌分化。此外，Akt与SIRT1之间的相互作用独立于N-Myc，并且在N-Myc被阻断时可驱动神经内分泌前列腺癌的发展。此外，SIRT1有助于肿瘤维持，靶向SIRT1可能会减轻雄激素剥夺期间的肿瘤负担。我们的研究结果表明，SIRT1是治疗干预的潜在靶点。
