Background
Epstein-Barr virus induced gene 3 (EBI3), a member of the IL-12 family, is known to be involved in malignant progression in a variety of cancers, but its role in melanoma is unclear. The
Conclusion
This study filled the blank on the involvement of EBI3 in melanoma, hinting the possibility of controlling EBI3 as a therapeutic strategy in the management of melanoma.
Methods
In this study, we used bioinformatics to analyze the expression of EBI3 in pan-cancer and verified its expression level in melanoma cells by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the effects of EBI3 knockdown on cell proliferation, migration and invasion were detected using the Cell Counting Kit-8 (CCK-8) and Transwell assays. Changes in immune-related cytokines were detected by ELISA, and macrophage polarization was observed using immunofluorescence. Finally, the phosphorylation levels of signaling pathways such as Smad3, STAT6 and cGAS-STING were analyzed by Western blot.
Results
EBI3 was evidently highly-expressed in melanoma, and silencing of EBI3 could visibly suppress the survival and migration/invasion of melanoma cells, concurrent with the increased levels of BAX and CDH1 and the decreased expressions of BCL2 and CDH2. Meanwhile, EBI3 knockdown diminished the phosphorylation levels of both Smad3 and STAT6 and the levels of immune response-relevant cytokines in melanoma cells, while aggravating the macrophage M1 polarization and the expression of cGAS, p-STING and p-IRE1 α in THP-1 monocyte-derived macrophages co-cultured with EBI3-silenced melanoma cells.