Abstract
hSNF2H partners with Rsf-1 to compose the Rsf complex to regulate gene expression. Recent studies indicated that hSNF2H was overexpressed in several human cancers. However, its expression pattern and biological mechanism in glioma remain unexplored. In this study, we found that hSNF2H was overexpressed in 32 % of glioma specimens. hSNF2H overexpression correlated with advanced tumor grade (p = 0.0338) and Rsf-1 positivity in glioma tissues (p = 0.016). Small interfering RNA (siRNA) knockdown was performed in A172 and U87 cell lines. MTT, colony formation assay, and cell cycle analysis showed that knockdown of hSNF2H inhibited cell proliferation, colony formation ability, and cell cycle transition. Matrigel invasion assay showed that hSNF2H depletion inhibited invasive ability of glioma cells. In addition, we demonstrated that hSNF2H depletion decreased temozolomide resistance of A172 and U87 cell lines and increased temozolomide induced apoptosis. Furthermore, hSNF2H depletion decreased cyclin D1, cyclin E, p-Rb, MMP2, cIAP1, Bcl-2 expression, and phosphorylation of IκBα and p65, suggesting hSNF2H regulates apoptosis through NF-κB pathway. Immunoprecipitation showed that hSNF2H could interact with Rsf-1 in both cell lines. To validate the involvement of Rsf-1, we checked the change of its downstream targets in Rsf-1 depleted cells. In Rsf-1 depleted cells, changes of cyclin E, Bcl-2, and p-IκBα were not significant using hSNF2H siRNA treatment. In conclusion, our study demonstrated that hSNF2H was overexpressed in human gliomas and contributed to glioma proliferation, invasion, and chemoresistance through regulation of cyclin E and NF-κB pathway, which is dependent on its interaction with Rsf-1.
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Siegel R, Naishadham D, Jemal A. Cancer statistics. CA Cancer J Clin. 2012;62:10–29.
Krupkova Jr O, Loja T, Redova M, Neradil J, Zitterbart K, et al. Analysis of nuclear nestin localization in cell lines derived from neurogenic tumors. Tumour Biol. 2011;32:631–9.
Zadran S, Amighi A, Otiniano E, Wong K, Zadran H. ENTPD5-mediated modulation of ATP results in altered metabolism and decreased survival in gliomablastoma multiforme. Tumour Biol. 2012;33:2411–21.
Kokavec J, Podskocova J, Zavadil J, Stopka T. Chromatin remodeling and SWI/SNF2 factors in human disease. Front Biosci. 2008;13:6126–34.
LeRoy G, Orphanides G, Lane WS, Reinberg D. Requirement of RSF and FACT for transcription of chromatin templates in vitro. Science. 1998;282:1900–4.
Poot RA, Dellaire G, Hulsmann BB, Grimaldi MA, Corona DF, et al. HuCHRAC, a human ISWI chromatin remodelling complex contains hACF1 and two novel histone-fold proteins. EMBO J. 2000;19:3377–87.
Strohner R, Nemeth A, Jansa P, Hofmann-Rohrer U, Santoro R, et al. NoRC--a novel member of mammalian ISWI-containing chromatin remodeling machines. EMBO J. 2001;20:4892–900.
Lazzaro MA, Picketts DJ. Cloning and characterization of the murine Imitation Switch (ISWI) genes: differential expression patterns suggest distinct developmental roles for Snf2h and Snf2l. J Neurochem. 2001;77:1145–56.
Chong S, Vickaryous N, Ashe A, Zamudio N, Youngson N, et al. Modifiers of epigenetic reprogramming show paternal effects in the mouse. Nat Genet. 2007;39:614–22.
Stopka T, Skoultchi AI. The ISWI ATPase Snf2h is required for early mouse development. Proc Natl Acad Sci U S A. 2003;100:14097–102.
Gigek CO, Lisboa LC, Leal MF, Silva PN, Lima EM, et al. SMARCA5 methylation and expression in gastric cancer. Cancer Invest. 2011;29:162–6.
Stopka T, Zakova D, Fuchs O, Kubrova O, Blafkova J, et al. Chromatin remodeling gene SMARCA5 is dysregulated in primitive hematopoietic cells of acute leukemia. Leukemia. 2000;14:1247–52.
Reis ST, Timoszczuk LS, Pontes-Junior J, Viana N, Silva IA, et al. The role of micro RNAs let7c, 100 and 218 expression and their target RAS, C-MYC, BUB1, RB, SMARCA5, LAMB3 and Ki-67 in prostate cancer. Clinics (Sao Paulo). 2013;68:652–7.
Sheu JJ, Choi JH, Yildiz I, Tsai FJ, Shaul Y, et al. The roles of human sucrose nonfermenting protein 2 homologue in the tumor-promoting functions of Rsf-1. Cancer Res. 2008;68:4050–7.
Sheu JJ, Guan B, Choi JH, Lin A, Lee CH, et al. Rsf-1, a chromatin remodeling protein, induces DNA damage and promotes genomic instability. J Biol Chem. 2010;285:38260–9.
Loyola A, Huang JY, LeRoy G, Hu S, Wang YH, et al. Functional analysis of the subunits of the chromatin assembly factor RSF. Mol Cell Biol. 2003;23:6759–68.
Li H, Zhang Y, Zhang Y, Bai X, Peng Y, et al. Rsf-1 overexpression in human prostate cancer, implication as a prognostic marker. Tumour Biol. 2014;35:5771–6.
Lin CY, Tian YF, Wu LC, Chen LT, Lin LC, et al. Rsf-1 expression in rectal cancer: with special emphasis on the independent prognostic value after neoadjuvant chemoradiation. J Clin Pathol. 2012;65:687–92.
Liu S, Dong Q, Wang E. Rsf-1 overexpression correlates with poor prognosis and cell proliferation in colon cancer. Tumour Biol. 2012;33:1485–91.
Choi JH, Sheu JJ, Guan B, Jinawath N, Markowski P, et al. Functional analysis of 11q13.5 amplicon identifies Rsf-1 (HBXAP) as a gene involved in paclitaxel resistance in ovarian cancer. Cancer Res. 2009;69:1407–15.
Qi XC, Xie DJ, Yan QF, Wang YR, Zhu YX, et al. LRIG1 dictates the chemo-sensitivity of temozolomide (TMZ) in U251 glioblastoma cells via down-regulation of EGFR/topoisomerase-2/Bcl-2. Biochem Biophys Res Commun. 2013;437:565–72.
Wagner L, Marschall V, Karl S, Cristofanon S, Zobel K, et al. Smac mimetic sensitizes glioblastoma cells to Temozolomide-induced apoptosis in a RIP1- and NF-kappaB-dependent manner. Oncogene. 2013;32:988–97.
Liu S, Shen H, Xu M, Liu O, Zhao L, et al. FRP inhibits ox-LDL-induced endothelial cell apoptosis through an Akt-NF-{kappa}B-Bcl-2 pathway and inhibits endothelial cell apoptosis in an apoE-knockout mouse model. Am J Physiol Endocrinol Metab. 2010;299:E351–363.
Chen GG, Liang NC, Lee JF, Chan UP, Wang SH, et al. Over-expression of Bcl-2 against Pteris semipinnata L-induced apoptosis of human colon cancer cells via a NF-kappa B-related pathway. Apoptosis. 2004;9:619–27.
Zhou AY, Shen RR, Kim E, Lock YJ, Xu M, et al. IKKepsilon-mediated tumorigenesis requires K63-linked polyubiquitination by a cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex. Cell Rep. 2013;3:724–33.
Sheu JJ, Choi JH, Guan B, Tsai FJ, Hua CH, et al. Rsf-1, a chromatin remodelling protein, interacts with cyclin E1 and promotes tumour development. J Pathol. 2013;229:559–68.
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The study was supported by the National Natural Science Foundation of China (No. 81000824, 81473285, and 81101402).
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Zhao, XC., An, P., Wu, XY. et al. Overexpression of hSNF2H in glioma promotes cell proliferation, invasion, and chemoresistance through its interaction with Rsf-1. Tumor Biol. 37, 7203–7212 (2016). https://doi.org/10.1007/s13277-015-4579-4
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DOI: https://doi.org/10.1007/s13277-015-4579-4