Department of Radiology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
Department of Pharmacy, The Affiliated Children's Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
Mol Med Rep. 2018 Feb;17(2):2901-2906. doi: 10.3892/mmr.2017.8257. Epub 2017 Dec 12.
Androgens have been recognized to be primary causative agents of prostate cancer. Following binding to the androgen receptor (AR), androgens serve important roles in the carcinogenesis of prostate cancers. ARs serve an important role during all stages of prostate cancer, and inhibiting their function may help to slow prostate cancer growth. In the present study, the AR gene was targeted in androgen‑positive prostate cancer cells using the clustered regularly interspaced short palindromic repeats‑associated protein (CRISPR/Cas) system. A total of three different single‑guide RNAs (sgRNAs) were designed according to the three different target sites in the AR gene. The optimal sgRNA with a specific target effect was effectively screened to cleave the AR gene in androgen‑positive prostate cancer cell lines, and to suppress the growth of androgen‑sensitive prostate cancer in vitro. The AR‑sgRNA‑guided CRISPR/Cas system was able to disrupt the AR at specific sites and inhibit the growth of androgen‑sensitive prostate cancer cells; further studies demonstrated that the decreased cell proliferation was due to cellular apoptosis. The results of the present study suggested that the CRISPR/Cas system may be a useful therapeutic strategy for the treatment of prostate cancer.
雄激素已被确认为前列腺癌的主要致病因素。雄激素与雄激素受体（AR）结合后，在前列腺癌的发生过程中发挥重要作用。AR 在前列腺癌的所有阶段都发挥着重要作用，抑制其功能可能有助于减缓前列腺癌的生长。在本研究中，使用簇状规律间隔短回文重复相关蛋白（CRISPR/Cas）系统靶向雄激素阳性前列腺癌细胞中的 AR 基因。根据 AR 基因中的三个不同靶位点设计了总共三种不同的单链向导 RNA（sgRNA）。有效筛选出具有特定靶向作用的最佳 sgRNA，以切割雄激素阳性前列腺癌细胞系中的 AR 基因，并抑制体外雄激素敏感型前列腺癌的生长。AR-sgRNA 指导的 CRISPR/Cas 系统能够在特定部位破坏 AR 并抑制雄激素敏感型前列腺癌细胞的生长；进一步的研究表明，细胞增殖减少是由于细胞凋亡所致。本研究结果表明，CRISPR/Cas 系统可能是治疗前列腺癌的一种有用的治疗策略。
