Overexpression of proteasomal activator PA28α serves as a prognostic factor in oral squamous cell carcinoma.

ABSTRACT

BACKGROUND: Despite recent advances in oral squamous cell carcinoma (OSCC) diagnosis and therapy, disease recurrence remains common and is strongly associated with mortality. It is therefore critical to identify new targets for both treatment and diagnostic purposes. We aimed at investigating the role of PA28α, a proteasomal activator in OSCC. METHODS: The expression of PA28α was examined in a panel of OSCC cell lines and tissues, associated with oncomine analysis. In a large OSCC patient cohort, the prognostic value of PA28α expression was evaluated. Primary clinical end points were recurrence-free and overall survival rate. Functional involvement of PA28α in OSCC was examined in both in vitro and in vivo models upon specific siRNA knockdown. RESULTS: PA28α was found to be overexpressed in OSCC cell lines and tumor tissues. High expression of PA28α was significantly associated with recurrence and poorer overall survival. Specific knockdown of PA28α inhibited OSCC cell proliferation, migration, invasion in vitro and reduced the growth of OSCC xenografts in vivo. Multivariate Cox regression analyses revealed PA28α as independent prognostic predictors. CONCLUSIONS: These results suggest that PA28α is involved in OSCC oncogenesis and may serve as a potential prognostic factor.