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SKA1基因表达下调抑制人膀胱癌细胞生长。

Downregulation of SKA1 Gene Expression Inhibits Cell Growth in Human Bladder Cancer.

作者信息

Tian Feng, Xing Xiaoxiao, Xu Feng, Cheng Wen, Zhang Zhengyu, Gao Jianping, Ge Jingping, Xie Hailong

机构信息

1 Department of Urology, Nanjing Jinling Hospital , Nanjing University School of Medicine, Nanjing, China .

2 Institute of Cancer Research, School of Medicine, University of South China , Hengyang, China .

出版信息

Cancer Biother Radiopharm. 2015 Sep;30(7):271-7. doi: 10.1089/cbr.2014.1715. Epub 2015 Jul 21.

Abstract

Spindle and kinetochore-associated protein 1 (SKA1), a component of microtubule-binding complex of kinetochore, is essential for proper chromosome segregation. Recently, SKA1 has been shown to be involved in malignant progression of several human cancers. However, its role in bladder cancer is still unknown. To evaluate the function of SKA1 in bladder cancer cells, the authors employed an RNA interference lentivirus system to deplete its expression in both BT5637 and T-24 bladder cancer cells. The cell proliferation was significantly decreased in both cell lines after SKA1 knockdown. Moreover, the colony formation capacity was impaired by SKA1 silencing. Flow cytometry analysis showed that depletion of SKA1 led to cell cycle arrest at S phase. Furthermore, knockdown of SKA1 in T-24 cells obviously downregulated the expressions of CDK4 and Cyclin D1, and alleviated the activations of ERK2 and AKT, conducive to cell growth inhibition. These findings suggested that knockdown of SKA1 could potently suppress bladder cancer cell proliferation in vitro and lentivirus-mediated silencing of SKA1 might serve as a novel strategy for gene therapy of bladder cancer.

摘要

纺锤体和动粒相关蛋白1(SKA1)是动粒微管结合复合体的一个组成部分,对染色体的正确分离至关重要。最近研究表明,SKA1参与了多种人类癌症的恶性进展。然而,其在膀胱癌中的作用仍不清楚。为了评估SKA1在膀胱癌细胞中的功能,作者采用RNA干扰慢病毒系统来降低其在BT5637和T-24膀胱癌细胞中的表达。SKA1敲低后,两种细胞系的细胞增殖均显著降低。此外,SKA1沉默削弱了集落形成能力。流式细胞术分析表明,SKA1缺失导致细胞周期停滞于S期。此外,T-24细胞中SKA1的敲低明显下调了CDK4和细胞周期蛋白D1的表达,并减轻了ERK2和AKT的激活,有利于抑制细胞生长。这些发现表明,敲低SKA1可有效抑制膀胱癌细胞的体外增殖,慢病毒介导的SKA1沉默可能成为膀胱癌基因治疗的新策略。

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