Overexpression of a Chromatin Remodeling Factor, RSF-1/HBXAP, Correlates with Aggressive Oral Squamous Cell Carcinoma

Abstract

RSF-1, also known as hepatitis B X-antigen associated protein (HBXAP), is a subunit of an ISWI chromatin remodeling complex, remodeling and spacing factor (RSF). Recent studies have provided new evidence that chromatin remodeling participates in the pathogenesis of neoplastic diseases by altering cell cycle regulation and gene expression. In this report, we studied the biological roles of RSF-1 in oral squamous cell carcinoma (OSCC), a highly invasive neoplastic disease. Based on IHC and quantitative real-time PCR, we demonstrated that RSF-1 expression could be detected in the majority of OSCC cases, and the levels were significantly higher in OSCC cells than in their normal counterparts. Moreover, expression levels of RSF-1 significantly correlated with the presence of angiolymphatic invasion, abnormal mitoses, metastasis, tumor recurrence, and advanced stage disease at presentation. Univariate and multivariate analyses showed a significant association of RSF-1 overexpression and worse overall survival in OSCC patients. RSF-1 knockdown remarkably decreased cellular proliferation and induced apoptosis in OSCC cells with high RSF-1 expression levels, but not in those without. Taken together, our results suggest that RSF-1 up-regulation is associated with several clinicopathological features of disease aggressiveness in OSCC patients, and RSF-1 plays an important role in maintaining cellular growth and survival in OSCC.