Cigarette smoking induces the activation of RIP2/caspase-12/NF- κ B axis in oral squamous cell carcinoma.

Cigarette smoking is one of the major risk factors for the occurrence and progression of oral squamous cell carcinoma (OSCC). Receptor-interacting protein 2 (RIP2) has been involved in mucosal immunity and homeostasis via a positive regulation of nuclear factor B (NF-B) transcription factor activity. Caspase-12 can bind to RIP2 and dampen mucosal immunity. However, the roles of RIP2/NF-B and caspase-12 in OSCC induced by cigarette smoking remain unknown. Herein, we investigated the effects of cigarette smoking on the RIP2/NF-B and caspase-12 in human OSCC tissues and OSCC cell lines (HSC-3). We first observed that RIP2 mediated NF-B activation and caspase-12 upregulation in OSCC patients with cigarette smoking and cigarette smoke extract (CSE)-treated HSC-3 cells, respectively. Moreover, we confirmed that the downregulation of RIP2 by siRNA resulted in the reduction of caspase-12 expression and NF-B activity in the presence of CSE treatment . In summary, our results indicated that cigarette smoking induced the activation of the RIP2/caspase-12/NF-B axis and it played an important role in the development of OSCC. The RIP2/caspase-12/NF-B axis could be a target for OSCC prevention and treatment in the future.