Hepatocellular carcinoma (HCC) is one of the most common malignancies with a high lethality rate. ZMIZ2 is a transcriptional co-activator implicated in various human diseases. However, the role and molecular mechanism of ZMIZ2 in HCC remains to be elucidated. The expression and prognostic value of ZMIZ2 in HCC was excavated from public databases and explored by bioinformatic analysis. Then the expression of ZMIZ2 and related genes was further validated by quantitative RT-PCR, western blotting, and immunohistochemistry. Loss and gain-of-function experiments were performed in vitro and in vivo to investigate the function of ZMIZ2 in HCC. In addition, transcriptome sequencing and immunoprecipitation was conducted to explore the potential molecular mechanisms of ZMIZ2. ZMIZ2 was highly expressed in HCC and associated with poor prognosis. Silencing ZMIZ2 significantly inhibited HCC cell proliferation, cell cycle process, migration, and invasion in vitro, and also inhibited the progression of HCC in vivo. Additionally, ZMIZ2 expression was correlated with immune cell infiltration in HCC samples. Somatic mutation analysis showed that ZMIZ2 and TP53 mutations jointly affected the progression of HCC. Mechanistically, ZMIZ2 interacted with LEF1 to regulate malignant progression of HCC by activating the Wnt/β-catenin pathway. ZMIZ2 was overexpressed in HCC and associated with poor prognosis. The overexpression of ZMIZ2 was corelated with malignant phenotype, and it facilitated HCC progression via LEF1-mediated activation of the Wnt/β-catenin pathway. Furthermore, ZMIZ2 could be served as a prognostic biomarker and a new therapeutic target for HCC.

中文翻译：

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ZMIZ2 通过 LEF1 介导的 Wnt/β-catenin 通路激活促进肝细胞癌进展

肝细胞癌（HCC）是最常见的恶性肿瘤之一，致死率很高。ZMIZ2 是一种转录共激活因子，与多种人类疾病有关。然而，ZMIZ2在HCC中的作用和分子机制仍有待阐明。从公共数据库中挖掘ZMIZ2在HCC中的表达和预后价值，并通过生物信息学分析探讨。然后通过定量RT-PCR、蛋白质印迹和免疫组化进一步验证ZMIZ2及相关基因的表达。在体外和体内进行功能丧失和获得实验，以研究 ZMIZ2 在 HCC 中的功能。此外，还进行了转录组测序和免疫沉淀来探索ZMIZ2的潜在分子机制。ZMIZ2 在 HCC 中高表达并与不良预后相关。沉默ZMIZ2在体外显着抑制HCC细胞增殖、细胞周期过程、迁移和侵袭，在体内也抑制HCC进展。此外，ZMIZ2 表达与 HCC 样本中的免疫细胞浸润相关。体细胞突变分析显示ZMIZ2和TP53突变共同影响HCC的进展。从机制上讲，ZMIZ2 与 LEF1 相互作用，通过激活 Wnt/β-catenin 通路来调节 HCC 的恶性进展。ZMIZ2 在 HCC 中过度表达并与不良预后相关。ZMIZ2 的过度表达与恶性表型相关，并且它通过 LEF1 介导的 Wnt/β-catenin 通路激活促进 HCC 进展。此外，ZMIZ2可以作为HCC的预后生物标志物和新的治疗靶点。