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YTHDF1通过增强肝癌细胞肿瘤干性及激活Wnt/β-catenin信号通路促进肝癌进展

YTHDF1 promotes hepatocellular carcinoma progression by increasing the stemness of HCC cells and activating the Wnt/β-catenin signaling pathway

    摘要
  • 摘要:
    目的 探讨m6A甲基化修饰识别蛋白YTH家族蛋白1（YTH domain family protein 1，YTHDF1）促进肝癌细胞肿瘤干性及激活Wnt/β-catenin信号通路促进肝癌进展的机制。
    方法 采用Western印迹法检测6组肝癌组织和癌旁肝组织中YTHDF1蛋白的表达情况。采用Western印迹法、RIP-PCR、qRT-PCR等检测β-catenin及其下游分子的表达。qRT-PCR、成球实验、克隆形成实验、CCK8等检测YTHDF1对肝癌细胞干性的影响。采用Kaplan-Meier生存曲线分析YTHDF1表达与肝癌患者临床预后的关系。
    结果 肝癌组织中YTHDF1的表达水平明显高于癌旁组织（P < 0.001）；过表达YTHDF1后，β-catenin及其下游分子的表达增加；过表达YTHDF1后，肝癌细胞的肿瘤干性明显上调、增殖能力显著增强；Kaplan-Meier生存曲线表明YTHDF1高表达的肝癌患者预后更差。
    结论 YTHDF1在肝癌组织中高表达，促进了β-catenin及其下游分子的表达，增强了肝癌细胞的干性，对肝癌患者的预后产生了不良影响。

     

    Abstract:
    Objective To explore the mechanism of YTH domain family protein 1(YTHDF1) promoting tumor stemness of hepatocellular carcinoma (HCC) cells and activating the Wnt/β-catenin signaling pathway to promote hepatocellular carcinoma progression.
    Methods Western blotting was used to detect the expression of YTHDF1 protein in 6 pairs of liver cancer tissues and adjacent liver tissues. Western-blotting, RIP-PCR, and qRT-PCR were used to detect the expression of β-catenin and its downstream molecules. qRT-PCR, sphere-forming assay, cell proliferation, and colony formation assays, and CCK8 assay were used to detect the carcinogenic effect of YTHDF1 in HCC cells. Kaplan-Meier survival curve was used to analyze the relationship between YTHDF1 and the clinical prognosis of HCC.
    Results The expression of YTHDF1 protein in HCC tissues was significantly higher than that in adjacent tissues (P < 0.001).The expression of β-catenin and its downstream molecules increased. The stemness markers of HCC cells were significantly up-regulated and the proliferation ability was significantly enhanced. Kaplan-Meier survival curve showed that patients with high expression of YTHDF1 had a poor prognosis.
    Conclusions The high expression of YTHDF1 in HCC tissue promotes the expression of β-catenin and its downstream molecules, the stemness of HCC cells, and adversely affects the prognosis of HCC patients.

     

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