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

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.

microRNA-340 Suppresses Tumorigenic Potential of Prostate Cancer Cells by Targeting High-Mobility Group Nucleosome-Binding Domain 5

“…In bladder cancer, high HMGN5 expression is positively correlated with the tumor grade and lymph node metastasis, and HMGN5 silencing suppresses cancer cell proliferation and invasion (Wahafu et al, 2011). Consistently, Ji et al (2012) reported that HMGN5 is strongly expressed in clear cell renal cell carcinoma tissues that were correlated with the tumor grade.…”

“…In addition, MMP9 promotes tumor metastasis by enhancing the cell invasion ability of tumor cells (Belotti et al, 2003). Previous studies reported that HMGN5 inhibition can impair the expressions of cyclin B1, Bcl-2, and MMP9 ( Jiang et al, 2010;Wahafu et al, 2011;Ji et al, 2012).…”

“…Overexpressed HMGN5 was found in high-metastatic breast cancer cells (Li et al, 2006). HMGN5 is also overexpressed in bladder cancer and clear cell renal cell carcinoma (Wahafu et al, 2011;Ji et al, 2012). Moreover, an early study has revealed that HMGN5 is found in prostate cancer tissues (Song et al, 2006).…”

KCNJ1 inhibits tumor proliferation and metastasis and is a prognostic factor in clear cell renal cell carcinoma

“…Protein concentration was measured using BCA Protein Assay Kit (CWBIO, China), and equal amounts of protein (20 μg) were separated in 12 % sodium dodecylsulfate (SDS)-polyacrylamide gels. Western blot analysis was performed according to a standard protocol as described previously [20]. The primary antibodies used in this study contained: anti-Flag, caspase9, caspase8, P53, Bcl-2, Bcl-xl, Bax, cleaved caspase 3, PARP, tubulin (Cell Signal Tech, USA), GAPDH, caspase3 (Protein Tech, USA), and KCNJ1 (Sigma, USA).…”

HMGB1 in health and disease

“…The expression of HMGN5 protein varies significantly between cells and tissues during embryonic development (Shirakawa et al, 2000). In addition, HMGN5 expression is upregulated with the development of several cancers, including squamous cell carcinoma, breast and bladder cancer, renal cell carcinoma, and gliomas (Gerlitz, 2010; Ji et al, 2012b; Li et al, 2006a; Qu et al, 2011; Tang et al, 2008b; Wahafu et al, 2011). Knockout of HMGN5 by RNAi inhibits cell proliferation and increases apoptosis in cancer cells (Chen et al, 2012b; Ji et al, 2012b; Zhang et al, 2012c).…”