The N7-methylguanosine (m7G), a modification at defined internal positions within tRNAs and rRNAs, is correlated with tumor progression. Methyltransferase like 1 (METTL1)/ WD repeat domain 4 (WDR4) mediated tRNA m7G modification, which could alter many oncogenic mRNAs translation to promote progress of multiple cancer types. However, whether and how the internal mRNA m7G modification is involved in tumorigenesis remains unclear. The immunohistochemistry assay was conducted to detect the expression of and in hepatocellular carcinoma (HCC) and the expression of both genes whether contributes to the prognosis of the survival rate of HCC patients Then, CCK8, colony formation assays and tumor xenograft models were conducted to determine the effects of WDR4 on HCC cells and Besides, dot blot assay, m7G-MeRIP-seq and RNA-seq analysis were conducted to determine whether WDR4 contributes to m7G modification and underlying mechanism in HCC cells. Finally, rescue and CO-IP assay were conducted to explore whether WDR4 and METTL1 proteins form a complex in Huh7 cells. WDR4 modulates m7G modification at the internal sites of tumor-promoting mRNAs by forming the WDR4-METTL1 complex. WDR4 knockdown downregulated the expression of mRNA and protein levels of METTL1 gene and thus further modulate the formation of WDR4-METTL1 complex indirectly. METTL1 expression was markedly correlated with WDR4 expression in HCC tissues. HCC patients with high expression of both genes had a poor prognosis. WDR4 may contribute to HCC pathogenesis by interacting with and regulating the expression of METTL1 to synergistically modulate the m7G modification of target mRNAs in tumor cells.

中文翻译：

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WDR4通过N7-甲基鸟苷调节并与METTL1相互作用促进HCC发病

N7-甲基鸟苷 (m7G) 是 tRNA 和 rRNA 内特定内部位置的修饰，与肿瘤进展相关。甲基转移酶样 1 (METTL1)/WD 重复结构域 4 (WDR4) 介导的 tRNA m7G 修饰，可以改变许多致癌 mRNA 的翻译，从而促进多种癌症类型的进展。然而，内部 mRNA m7G 修饰是否以及如何参与肿瘤发生仍不清楚。采用免疫组化法检测肝细胞癌（HCC）中 和 的表达情况以及这两种基因的表达是否有助于 HCC 患者生存率的预后，然后进行 CCK8、集落形成实验和肿瘤异种移植模型来确定此外，还进行了斑点印迹分析、m7G-MeRIP-seq 和 RNA-seq 分析，以确定 WDR4 是否有助于 HCC 细胞中的 m7G 修饰及其潜在机制。最后，进行救援和CO-IP实验以探讨WDR4和METTL1蛋白是否在Huh7细胞中形成复合物。 WDR4 通过形成 WDR4-METTL1 复合物来调节促肿瘤 mRNA 内部位点的 m7G 修饰。 WDR4敲低下调METTL1基因的mRNA表达和蛋白水平，从而进一步间接调节WDR4-METTL1复合物的形成。 HCC 组织中 METTL1 表达与 WDR4 表达显着相关。这两种基因高表达的肝癌患者预后较差。 WDR4 可能通过与 METTL1 相互作用并调节 METTL1 的表达，协同调节肿瘤细胞中靶标 mRNA 的 m7G 修饰，从而促进 HCC 发病机制。