MATR3 promotes liver cancer progression by suppressing DHX58–mediated type I interferon response

IF 9.1 1区 医学 Q1 ONCOLOGY Cancer letters Pub Date : 2024-09-12 DOI:10.1016/j.canlet.2024.217231
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Abstract

MATR3 is a nuclear matrix protein implicated in various cancers; however, its specific role in tumor progression remains unclear. The study utilized the TCGA database to reveal that MATR3 expression is upregulated in liver cancer and is correlated with poor prognosis. Functionally, MATR3 promoted liver cancer cell proliferation and metastasis. Comprehensive RNA sequencing analysis showed that MATR3 significantly affected the type I IFN signaling pathway and DHX58 is a downstream target of MATR3. Further experiments showed that MATR3 bound to DHX58 mRNA through its RRM structural domain and recruited YTHDF2, an m6A reader, leading to degradation of DHX58 mRNA and suppression of the type I IFN signaling pathway. The knockout of MATR3 in liver cancer cells triggered a natural immune response that stimulated CD8+ T cells to eliminate liver cancer cells. This study demonstrated that MATR3 downregulates type I IFN signaling in liver cancer cells through m6A modification and inhibits immune cell infiltration within tumors. These findings expand our understanding of the role of MATR3 in liver cancer.

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MATR3 通过抑制 DHX58 介导的 I 型干扰素反应促进肝癌进展
MATR3是一种与多种癌症有关联的核基质蛋白,但它在肿瘤进展中的具体作用仍不清楚。研究利用TCGA数据库发现,MATR3在肝癌中表达上调,并与预后不良相关。在功能上,MATR3能促进肝癌细胞的增殖和转移。全面的RNA测序分析表明,MATR3显著影响I型IFN信号通路,而DHX58是MATR3的下游靶点。进一步的实验表明,MATR3通过其RRM结构域与DHX58 mRNA结合,并招募m6A阅读器YTHDF2,导致DHX58 mRNA降解,抑制I型IFN信号通路。在肝癌细胞中敲除 MATR3 会引发自然免疫反应,刺激 CD8+ T 细胞消灭肝癌细胞。这项研究证明,MATR3 通过 m6A 修饰下调肝癌细胞的 I 型 IFN 信号,并抑制肿瘤内免疫细胞的浸润。这些发现拓展了我们对 MATR3 在肝癌中作用的认识。
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来源期刊
Cancer letters
Cancer letters 医学-肿瘤学
CiteScore
17.70
自引率
2.10%
发文量
427
审稿时长
15 days
期刊介绍: Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research. Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy. By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.
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