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核小体结合蛋白NSBP1在人膀胱癌中高表达,并促进膀胱癌细胞的增殖和侵袭。

The nucleosome binding protein NSBP1 is highly expressed in human bladder cancer and promotes the proliferation and invasion of bladder cancer cells.

作者信息

Wahafu Wasilijiang, He Zhi-Song, Zhang Xiao-Yu, Zhang Cui-Jian, Yao Kun, Hao Han, Song Gang, He Qun, Li Xue-Song, Zhou Li-Qun

机构信息

Department of Urology, Peking University First Hospital, Beijing, China.

出版信息

Tumour Biol. 2011 Oct;32(5):931-9. doi: 10.1007/s13277-011-0195-0. Epub 2011 Jun 22.

Abstract

NSBP1 is a recently identified member of the HMGN protein family which binds to nucleosomes and regulates gene transcription through chromatin remodeling. In this study, we aimed to investigate the potential role of NSBP1 in human bladder cancer. We examined NSBP1 expression in 114 surgically removed bladder cancer specimens as well as 11 human bladder cell lines by immunohistochemistry and Western blot analysis, and found that NSBP1 level was correlated with the increased tumor grade and pathologic stage, and lymph node metastasis. RNAi-mediated knockdown of NSBP1 in EJ cells, a bladder cancer cell line that overexpressed NSBP1, resulted in moderate decrease of cell viability, moderate blockage of cell cycle at G2/M phase, and decreased cyclin B1 expression, but had no effects on apoptosis. Moreover, NSBP1 knockdown led to reduced activity of MMP-9 but not MMP-2. Taken together, these results suggest that NSBP1 promotes the viability of bladder cancer cells through increased cell proliferation but not decreased apoptosis, and increases the invasion ability of metastatic bladder cancer cells through the upregulation of MMP-9 activity. Our findings not only provide a molecular understanding of the role of NSBP1 in bladder cancer, but also suggest NSBP1 RNAi as a novel therapeutic approach for bladder cancer.

摘要

NSBP1是HMGN蛋白家族中最近鉴定出的成员,它与核小体结合并通过染色质重塑调节基因转录。在本研究中,我们旨在探究NSBP1在人类膀胱癌中的潜在作用。我们通过免疫组织化学和蛋白质印迹分析检测了114例手术切除的膀胱癌标本以及11种人类膀胱细胞系中的NSBP1表达,发现NSBP1水平与肿瘤分级增加、病理分期及淋巴结转移相关。在过表达NSBP1的膀胱癌细胞系EJ细胞中,RNA干扰介导的NSBP1敲低导致细胞活力适度下降、细胞周期在G2/M期适度阻滞、细胞周期蛋白B1表达降低,但对细胞凋亡无影响。此外,NSBP1敲低导致MMP-9活性降低,但对MMP-2无影响。综上所述,这些结果表明NSBP1通过增加细胞增殖而非减少细胞凋亡来促进膀胱癌细胞的活力,并通过上调MMP-9活性增加转移性膀胱癌细胞的侵袭能力。我们的研究结果不仅提供了对NSBP在膀胱癌中作用的分子理解,还表明NSBP1 RNA干扰作为一种新的膀胱癌治疗方法。

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