The E3 Ubiquitin Ligase SIAH2 Is a Prosurvival Factor Overexpressed in Oral Cancer

Background: This study aimed at investigating the expression and functional significance of seven in absentia homologues 2 (SIAH2), an E3 ubiquitin ligase, in oral squamous cell carcinoma (OSCC). Materials and Methods: Comparative genomic hybridization and real-time PCR were performed to examine the amplification of SIAH2 gene in clinical specimens of OSCC tissues. Expression of SIAH2 mRNA and protein was examined by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical assays, respectively. Apoptosis was examined by annexing V staining and Poly (ADP-ribose) polymerase (PARP) cleavage, with or without sienna-mediated SIAH2 knockdown. The expression of p.53 was analyzed by immunoblotting. Results: Levels of SIAH2 DNA and mRNA were significantly greater in clinical OSCC specimens and in cultured OSCC cells, which also stained positively for the SAIH2 protein. Knockdown of SIAH2 led to growth suppression and apoptosis induction in a p53-independent mechanism. Conclusion: These results revealed a tight correlation of SIAH2 overexpression with OSCC and suggest an oncogenic role of SIAH2 in oral cancer.