Role of type I- and type II-interferon in expression of melanoma differentiation-associated gene-5 in HSC-3 oral squamous carcinoma cells

Melanoma differentiation-associated gene 5 (MDA-5) and retinoic acid-inducible gene-I (RIG-I) are members of DExH family of proteins, and known to play important roles in antiviral responses to induce type I interferons (IFNs). MDA-5 has been thought to sense RNA virus with long (>1 kb) double-stranded RNA. However, MDA-5 is also induced by type II IFN that is involved in acquired immunity, suggesting that role of MDA-5 remains to be elucidated. In addition, no study regarding MDA-5 in oral region has been performed. Here we investigated the role of MDA-5 in HCS-3 squamous carcinoma cells derived from oral epithelial cells. Treatment of HCS-3 cells with IFN-alpha 2b or IFN-gamma significantly induced MDA-5 as well as RIG-I. IFN-a2b exerted anti-proliferative effect in HSC-3 cells while no such effect was observed in the cells treated with IFN-gamma. MDA-5 is known to be associated with tumor cell growth in melanoma. However, overexpression of MDA-5 did not alter the proliferation in HSC-3 cells, indicating that MDA-5 is unrelated to the cell growth in this type of cells. We conclude that MDA-5 is induced by both type I- and type II-IFNs in HSC-3 cells, and this suggests MDA-5 may play a role in immune responses in oral cavity.