Stable suppression of tumorigenicity by CypA-targeted RNAi in oral cancer

Objectives: Cyclophilin A (CypA) was recently reported to be overexpressed in oral squamous cell carcinoma, and represents a potentially novel therapeutic target. In the present study, we sought to determine the potential of CypA-targeted gene silencing in inhibiting cellular growth and tumorigenicity in a oral cancer cell line, UM1. Methods: Stable RNA interference (RNAi)–mediated knockdown of CypA was established in UM1 cells. Cell growth and several transformed properties were investigated. Results: The stable expression of CypA-specific small interfering RNA constructs in UM1 cells significantly reduced cellular proliferation, colony formation, migration, and invasion but strongly enhanced the apoptotic response induced by serum depletion. Furthermore, CypA depletion differentially regulated several proapoptotic and antiapoptotic genes. Conclusions: These results strongly suggest that CypA plays an important role not only in tumorigenesis but also in the maintenance of the transformed phenotype in oral cancer cells. Hence, CypA may serve as a promising therapeutic target, particularly for oral squamous cell carcinoma. Supported by Oral and Maxillofacial Surgery Foundation.