RIG-I acts as a tumor suppressor in melanoma via regulating the activation of MKK/p38MAPK signaling pathway

Abstract Background Studies have indicated that RIG-I may act as a tumor suppressor and participate in the tumorigenesis of some malignant diseases. However, RIG-I induces distinct cellular responses via different downstream signaling pathways depending on the cell type. The aim of this study was to investigate the biological function and underlying molecular mechanism of RIG-I in the tumorigenesis of melanoma. Methods We conducted RIG-I knockout and RIG-I overexpressing B16-F10 melanoma cell line, and further analyzed the RIG-I mediated change of tumor biology behaviors in spontaneous and poly I:C induced RIG-I activation status. Cell proliferation, cell cycle, apoptosis and migration were detected by CCK-8 assay, BrdU incorporation, Annexin V-PI staining assay and transwell assay, respectively. In vivo tumorigenicity was evaluated by tumor xenograft growth in nude mice and subsequently Ki67 staining and TUNEL assay. Furthermore, Western blot was utilized to explore the underlying mechanism of RIG-I in melanoma cells. Results Our data showed that RIG-I promotes the apoptosis and inhibits the proliferation by G1 phase cell-cycle arrest in B16-F10 melanoma cell line. Mechanically, RIG-I could induce the phosphorylation level of p38 MAPK and MAPK kinase MKK3/MKK4. Conclusion The current study demonstrated that RIG-I suppressed the development of melanoma via regulating the activity of MKK/p38 MAPK signaling pathway, which will be useful in the research of novel therapeutic targets for this malignant disease.