文章：

RNF149通过其E3泛素连接酶活性促进肝细胞癌进展

RNF149 Promotes HCC Progression through Its E3 Ubiquitin Ligase Activity

原文发布日期：29 October 2023

DOI: 10.3390/cancers15215203

类型: Article

开放获取: 是

英文摘要：

Hepatocellular carcinoma (HCC) accounts for over 80% of cases among liver cancer, with high incidence and poor prognosis. Thus, it is of valuable clinical significance for discovery of potential biomarkers and drug targets for HCC. In this study, based on the proteomic profiling data of paired early-stage HCC samples, we found that RNF149 was strikingly upregulated in tumor tissues and correlated with poor prognosis in HCC patients, which was further validated by IHC staining experiments of an independent HCC cohort. Consistently, overexpression of RNF149 significantly promoted cell proliferation, migration, and invasion of HCC cells. We further proved that RNF149 stimulated HCC progression via its E3 ubiquitin ligase activity, and identified DNAJC25 as its new substrate. In addition, bioinformatics analysis showed that high expression of RNF149 was correlated with immunosuppressive tumor microenvironment (TME), indicating its potential role in immune regulation of HCC. These results suggest that RNF149 could exert protumor functions in HCC in dependence of its E3 ubiquitin ligase activity, and might be a potential prognostic marker and therapeutic target for HCC treatment.

摘要翻译： 

肝细胞癌（HCC）占肝癌病例的80%以上，具有高发病率与不良预后。因此，发现HCC的潜在生物标志物和药物靶点具有重要临床意义。本研究基于配对早期HCC样本的蛋白质组学分析数据，发现RNF149在肿瘤组织中显著上调，且与HCC患者不良预后相关，这一结果在独立HCC队列的免疫组化染色实验中得到进一步验证。一致的是，过表达RNF149显著促进了HCC细胞的增殖、迁移和侵袭能力。我们进一步证明RNF149通过其E3泛素连接酶活性驱动HCC进展，并鉴定出DNAJC25是其新底物。此外，生物信息学分析显示RNF149高表达与免疫抑制性肿瘤微环境相关，提示其在HCC免疫调控中的潜在作用。这些结果表明RNF149可能依赖其E3泛素连接酶活性在HCC中发挥促癌功能，有望成为HCC治疗的潜在预后标志物和治疗靶点。

原文链接：

RNF149 Promotes HCC Progression through Its E3 Ubiquitin Ligase Activity