文章：

下调TMEM220可促进肝细胞癌的肿瘤进展

Downregulation of TMEM220 promotes tumor progression in Hepatocellular Carcinoma 

原文发布日期：2021-07-28 

英文摘要：

During the process of long-term carcinogenesis, cells accumulate many mutations. Deregulated genes expression causes profound changes in cell proliferation, which is one of the hallmarks of HCC. A comprehensive understanding of these changes will contribute to the molecular mechanism of HCC progression. Through clinical sample analysis, we found that TMEM220 is downregulated in tumor and lower levels of TMEM220 is associated with poor prognosis in HCC patients. Through overexpressing TMEM220 in HCC cell lines, we found that the proliferation of cancer cells was significantly slowed down and metastasis was significantly reduced. For further study of its molecular mechanism, we performed a reverse-phase protein array (RPPA). The results suggest that phenotypic changes caused by TMEM220 in HCC cells might be associated with FOXO and PI3K-Akt pathways. Mechanism studies showed that overexpression of TMEM220 could regulate β-catenin and FOXO3 transcriptional activity by altering their subcellular localization, affecting the expression of downstream gene p21 and SNAIL, and ultimately reducing the progression of HCC. Altogether, our study proposes a working model in which upregulation of TMEM220 expression alters the genes expression involved in cell proliferation, thereby inhibiting HCC progression, which suggests that TMEM220 might serve as a clinical biomarker. 

摘要翻译： 

在长期致癌过程中，细胞会积累多种基因突变。基因表达失调导致细胞增殖功能发生深刻变化，这是肝细胞癌（HCC）的典型特征之一。全面理解这些变化有助于揭示HCC进展的分子机制。通过临床样本分析，我们发现TMEM220在肿瘤组织中表达下调，且其低表达水平与HCC患者不良预后相关。通过在HCC细胞系中过表达TMEM220，我们发现癌细胞增殖速度显著减慢，转移能力明显减弱。为深入研究其分子机制，我们采用反相蛋白阵列（RPPA）技术进行分析。结果表明TMEM220在HCC细胞中引起的表型变化可能与FOXO和PI3K-Akt通路相关。机制研究表明，过表达TMEM220可通过改变β-连环蛋白和FOXO3的亚细胞定位来调节其转录活性，影响下游基因p21和SNAIL的表达，最终延缓HCC进展。我们的研究提出了一个工作模型：TMEM220表达上调可改变细胞增殖相关基因的表达，从而抑制HCC进展，这表明TMEM220可能作为临床生物标志物。

原文链接：

Downregulation of TMEM220 promotes tumor progression in Hepatocellular Carcinoma