Overexpression of hSNF2H in glioma promotes cell proliferation, invasion, and chemoresistance through its interaction with Rsf-1

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.

Remodeling and spacing factor 1 overexpression is associated with poor prognosis in renal cell carcinoma

“…The results, suggesting that high RSF1 expression indicates a poor prognosis of RCC, are consistent with data in ovarian, prostate and hepatocellular cancer (17,18,21). The results may be explained by previous studies demonstrating that RSF1 promotes tumor cell proliferation and invasion (10,13,14,16). All of these results together suggest that RSF1 is an important oncogene in RCC.…”

“…Davidson et al indicated that the compared with low expression of RSF1, overexpression and amplification of RSF1 predicted a decreased survival in patients with ovarian cancer (21), similar to Erb-B2 receptor tyrosine kinase 2 in breast cancer (27) and MYCN proto-oncogene, BHLH transcription factor in neuroblastoma (28). It is plausible that RSF1 gene amplification and overexpression in tumor cells disrupts the homeostatic kinetics in the chromatin remodeling machinery and alters gene regulation, consequently facilitating tumorigenesis (10,29,30).…”

“…Chromatin remodeling is a basic process in multiple critical biological activities, including nucleic acid synthesis, transcriptional regulation, DNA repair, methylation and recombination (7). Cancer may be caused by mutations of any of the chromatin remodeling key proteins, since this will result in the abnormal expression of genes (8)(9)(10). RSF1 is overexpressed and exhibits gene amplification in multiple solid tumors, including breast cancer, ovarian cancer and oral squamous cell carcinoma (11)(12)(13).…”

Rsf-1 Influences the Sensitivity of Non-Small Cell Lung Cancer to Paclitaxel by Regulating NF-κB Pathway and Its Downstream Proteins

“…It is well defined that Rsf-1 contributes to chemoresistance in many cancers through activation of the NF-κB pathway [18, 19, 23, 25]. Rsf-1 knockout decreased the protein levels of p-P65, BcL2, CFLAR, and XIAP in H1299 and H460 cells, confirming that Rsf-1 regulates the activation of NF-κB and the expression of the genes downstream of NF-κB complex [23, 25].…”

“…Rsf-1 knockout decreased the protein levels of p-P65, BcL2, CFLAR, and XIAP in H1299 and H460 cells, confirming that Rsf-1 regulates the activation of NF-κB and the expression of the genes downstream of NF-κB complex [23, 25]. Inhibition of the NF-κB pathway by helenalin decreased the protein levels of p-P65, BcL2, CFLAR, and XIAP in these cells without altering Rsf-1 protein levels, suggesting that Rsf-1 acts on the NF-κB pathway at a point no further downstream from the site of helenalin inhibition.…”