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RNA 结合基序蛋白 28 通过改善肝细胞癌中的 STAT3 翻译促进血管生成。

RNA-binding motif protein 28 enhances angiogenesis by improving STAT3 translation in hepatocellular carcinoma.

机构信息

Department of Gastroenterology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, 225300, PR China.

Department of Hepatobiliary Surgery, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, 225300, PR China.

出版信息

Cancer Lett. 2024 Nov 1;604:217191. doi: 10.1016/j.canlet.2024.217191. Epub 2024 Aug 22.

DOI:10.1016/j.canlet.2024.217191
PMID:39181434
Abstract

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor characterized by extensive angiogenesis. However, the underlying mechanisms of HCC pathogenesis remain unclear. Previous studies have shown that RNA-binding proteins (RBPs) are implicated in HCC pathogenesis. In this study, we observed that increased RBM28 expression in HCC tissues was positively correlated with tumor microvascular density and negatively correlated with patient prognosis. Overexpression of RBM28 in HCC cells promoted tubule formation in human umbilical vein endothelial cells, whereas inhibition of RBM28 had the opposite effect, furthermore, the role of RBM28 in the progression of HCC was assessed using transgenic mouse models and chemically induced HCC models. We used various molecular assays and high-throughput detection methods to evaluate the role of RBM28 in promoting angiogenesis in HCC. Increased RBM28 expression in HCC directly binds to STAT3 mRNA, recruiting EIF4E to increase STAT3 expression and enhancing the secretion and expression of vascular endothelial growth factor A; consequently, promoting neovascularization in HCC. The potential of RBM28 as a viable diagnostic and therapeutic target for HCC was assessed using multi-cohort clinical samples and animal models. In summary, our results provide insights into the pathogenesis, clinical diagnosis, and treatment of HCC.

摘要

肝细胞癌(HCC)是一种常见的恶性肿瘤,其特征为广泛的血管生成。然而,HCC 发病机制的潜在机制仍不清楚。先前的研究表明,RNA 结合蛋白(RBPs)与 HCC 的发病机制有关。在这项研究中,我们观察到 HCC 组织中 RBM28 表达的增加与肿瘤微血管密度呈正相关,与患者预后呈负相关。RBM28 在 HCC 细胞中的过表达促进了人脐静脉内皮细胞管的形成,而 RBM28 的抑制则有相反的效果,此外,还使用转基因小鼠模型和化学诱导的 HCC 模型评估了 RBM28 在 HCC 进展中的作用。我们使用各种分子测定和高通量检测方法来评估 RBM28 在促进 HCC 血管生成中的作用。HCC 中 RBM28 表达的增加直接与 STAT3 mRNA 结合,招募 EIF4E 以增加 STAT3 的表达,并增强血管内皮生长因子 A 的分泌和表达;从而促进 HCC 中的新生血管形成。使用多队列临床样本和动物模型评估了 RBM28 作为 HCC 可行的诊断和治疗靶点的潜力。总之,我们的研究结果为 HCC 的发病机制、临床诊断和治疗提供了新的思路。

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