MX2 mediates establishment of interferon response profile, regulates XAF1, and can sensitize melanoma cells to targeted therapy

Abstract

MX2 is an interferon inducible gene that is mostly known for its antiviral activity. We have previously demonstrated that MX2 is also associated with the tumorigenesis process in melanoma. However, it remains unknown which molecular mechanisms are regulated by MX2 in response to interferon signaling in this disease. Here, we report that MX2 is necessary for the establishment of an interferon‐induced transcriptional profile partially through regulation of STAT1 phosphorylation and other interferon‐related downstream factors, including proapoptotic tumor suppressor XAF1. MX2 and XAF1 expression tightly correlate in both cultured melanoma cell lines and in patient‐derived primary and metastatic tumors, where they also are significantly related with survival. MX2 mediates IFN growth‐inhibitory signals in both XAF1 dependent and independent ways and in a cell type and context‐dependent manner. Higher MX2 expression renders melanoma cells more sensitive to targeted therapy drugs such as vemurafenib and trametinib; however, this effect is XAF1 independent. In summary, we uncovered a new mechanism in the complex regulation of interferon signaling in melanoma that can influence both survival and response to therapy.

Immunologically active ferumoxytol-poly(I : C) nanomaterials inhibit metastatic melanoma by regulating myeloid-derived suppressor cell differentiation

“…4C and Table S1†). Additionally, it was observed that the treatment caused an increase in the expression of anti-tumor genes, including Sox7 , 38 Xaf1 , 39 and B2m 40 (Fig. 4C and Table S1†).…”

The m6A-regulation and single cell effect pattern in sunitinib resistance on clear cell renal cell carcinoma: Identification and validation of targets

“…Liu and their colleagues demonstrated that the SLC2A3 could lead to the reduction of vitamin C uptake, therefore inhibiting leukemia development (Liu et al, 2020). Juraleviciute and their colleagues noticed that the MX2 could regulate the XAF1 and make the melanoma cells sensitive to targeted therapy (Juraleviciute et al, 2021). Wang and their colleagues found that the MX2 could suppress the glioblastoma progression through ERK/P38/NF-κB signaling (Wang et al, 2019b).…”

MX2: Identification and systematic mechanistic analysis of a novel immune-related biomarker for systemic lupus erythematosus

“…It can exert antiviral effects through IRF-3 and IRF-7 without involving IFN-γ signaling ( 48 ). In addition, MX2 may also modulate XAF1 to increase the sensitivity of melanoma cells to targeted therapies, which may be related to immune responses ( 49 ). Moreover, MX2 exerts immune effects by mediating multiple immune cells.…”