RNA 结合基调蛋白 28 通过改善肝细胞癌中 STAT3 的翻译促进血管生成。

IF 9.1 1区 医学 Q1 ONCOLOGY Cancer letters Pub Date : 2024-08-22 DOI:10.1016/j.canlet.2024.217191
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引用次数: 0

摘要

肝细胞癌(HCC)是一种以广泛血管生成为特征的常见恶性肿瘤。然而,HCC 发病的内在机制仍不清楚。以往的研究表明,RNA 结合蛋白(RBPs)与 HCC 发病机制有关。本研究观察到,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。此外,我们还利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。我们使用了多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 表达的增加可直接与 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 中血管的新生。我们利用多队列临床样本和动物模型评估了 RBM28 作为 HCC 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见解。
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RNA-binding motif protein 28 enhances angiogenesis by improving STAT3 translation in hepatocellular carcinoma

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.

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来源期刊
Cancer letters
Cancer letters 医学-肿瘤学
CiteScore
17.70
自引率
2.10%
发文量
427
审稿时长
15 days
期刊介绍: Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research. Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy. By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.
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