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The following is a summary of “MATR3 Promotes Liver Cancer Progression by Suppressing DHX58–Mediated Type I Interferon Response,” published in the September 2024 issue of Oncology by Xiao et al.

MATR3, a nuclear matrix protein, has been implicated in various cancers, yet its specific role in tumor progression remains poorly defined. This study employed the TCGA database to demonstrate that MATR3 expression is significantly elevated in liver cancer and correlates with adverse prognostic outcomes. Functional assays revealed that MATR3 facilitates liver cancer cell proliferation and metastasis. 

Through comprehensive RNA sequencing, it was identified that MATR3 influences the type I interferon (IFN) signaling pathway, with DHX58 emerging as a key downstream target. Mechanistic investigations revealed that MATR3 binds to DHX58 mRNA via its RNA recognition motif (RRM) domain, subsequently recruiting YTHDF2. This m6A reader protein leads to DHX58 mRNA degradation and attenuation of the type I IFN signaling pathway. This suppression of type I IFN signaling was further associated with reduced immune cell infiltration within the tumor microenvironment. Notably, the knockout of MATR3 in liver cancer cells elicited a robust natural immune response, activating CD8+ T cells to target and eliminate tumor cells. These findings elucidate that MATR3 mediates immune evasion in liver cancer by modulating m6A modification and inhibiting the type I IFN signaling pathway. This study enhances the understanding of MATR3’s role in liver cancer and highlights its potential as a therapeutic target for improving immune-based treatment strategies.

Source: sciencedirect.com/science/article/pii/S0304383524006268