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SMC1A在体外和体内促进前列腺癌的生长和迁移。

SMC1A promotes growth and migration of prostate cancer in vitro and in vivo.

作者信息

Pan Xiu-Wu, Gan Si-Shun, Ye Jian-Qing, Fan Ying-Hui, Hong Υi, Chu Chuan-Min, Gao Yi, Li Lin, Liu Xi, Chen Lu, Huang Yi, Xu Hong, Ren Ji-Zhong, Yin Lei, Qu Fa-Jun, Huang Hai, Cui Xin-Gang, Xu Dan-Feng

机构信息

Department of Urinary Surgery, Third Affiliated Hospital, Second Military Medical University, Shanghai 201805, P.R. China.

Department of Anesthesiology, Renji Hospital, Shanghai Jiaotong University, Shanghai 200127, P.R. China.

出版信息

Int J Oncol. 2016 Nov;49(5):1963-1972. doi: 10.3892/ijo.2016.3697. Epub 2016 Sep 19.

Abstract

Structural maintenance of chromosome 1 alpha (SMC1A) gene has been reported to be related to tumor development in some types of human cancers. However, the misregulation of SMC1A and its functions in castration-resistant prostate cancer (CRPC) have not been well understood. In the present study, we found that SMC1A was elevated in androgen-independent PCa cell lines PC-3 and DU-145 compared to androgen sensitive LNCap and 22RV1 cells by qPCR and western blot assay. Knockdown of SMC1A inhibited cell growth, colony formation and cell migration abilities of PC-3 and DU145 cells by MTT, colony formation and transwell assays, and affected cell cycle progression in PC-3 and DU145 cells by flow cytometry. Moreover, SMC1A knockdown significantly reduced tumor growth in vivo in a nude mouse model. Additionally, we also found that the expression of SMC1A gene was higher in prostate cancer tissues than in the adjacent normal tissues by immunohistochemical staining, and was positively correlated to tumor metastasis and recurrence by Oncomine database mining. Taken together, the present study indicates that SMC1A may play an important role in malignant transformation of PCa under conditions of androgen deprivation and act as a new target for PCa diagnosis and treatment.

摘要

据报道,染色体结构维持蛋白1α(SMC1A)基因与某些类型的人类癌症的肿瘤发展有关。然而,SMC1A的失调及其在去势抵抗性前列腺癌(CRPC)中的功能尚未得到充分了解。在本研究中,我们通过qPCR和蛋白质印迹分析发现,与雄激素敏感的LNCap和22RV1细胞相比,雄激素非依赖性前列腺癌细胞系PC-3和DU-145中的SMC1A水平升高。通过MTT、集落形成和Transwell实验,敲低SMC1A抑制了PC-3和DU145细胞的细胞生长、集落形成和细胞迁移能力,并通过流式细胞术影响了PC-3和DU145细胞的细胞周期进程。此外,在裸鼠模型中,敲低SMC1A显著降低了体内肿瘤生长。另外,我们还通过免疫组织化学染色发现,前列腺癌组织中SMC1A基因的表达高于相邻正常组织,并且通过Oncomine数据库挖掘发现其与肿瘤转移和复发呈正相关。综上所述,本研究表明,SMC1A可能在雄激素剥夺条件下的前列腺癌恶性转化中起重要作用,并可作为前列腺癌诊断和治疗的新靶点。

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