外泌体 circPVT1 通过激活 Rap1b-VEGFR2 信号通路促进喉癌的血管生成。

IF 3.3 3区 医学 Q2 ONCOLOGY
Kexing Lyu, Bingjie Tang, Bixue Huang, Zhenglin Xu, Tesi Liu, Ruihua Fang, Yun Li, Yi Chen, Lin Chen, Minjuan Zhang, Lifan Chen, Wenbin Lei
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引用次数: 0

摘要

喉癌(LC)是第二大最常见的头颈部癌症,全球 5 年生存率不断下降。环状 RNA 基于其独特的生物生成机制和广泛的调控作用,以不同的方式调控癌症的发展。然而,目前关于外泌体环状 RNA 如何参与喉癌发展的研究很少。在这里,我们证明了circPVT1是一种环状RNA,来源于研究较多的长非编码RNA PVT1,它与喉癌的疾病进展相关,并在体内和体外促进血管生成。从机理上讲,circPVT1 被载入 LC 细胞分泌的外泌体,并被血管上皮细胞吸收。通过吸收 miR-30c-5p,外泌体 circPVT1 可促进 Rap1b 的表达,从而显著增强 VEGFR2 和 PI3K/AKT 通路的激活,最终诱导血管生成。此外,我们的异种移植模型表明,shRNA-circPVT1 和西妥昔单抗的组合在抑制肿瘤生长和血管生成方面表现出很高的疗效。总之,这些发现揭示了外泌体环状 RNA 介导的血管生成调节的新机制,并为在 LC 患者中测试这种类似的组合提供了临床前依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exosomal circPVT1 promotes angiogenesis in laryngeal cancer by activating the Rap1b-VEGFR2 signaling pathway.

Laryngeal cancer (LC) is the second most common head and neck cancer and has a decreasing 5-year survival rate worldwide. Circular RNAs (circRNAs) regulate cancer development in diverse ways based on their distinct biogenesis mechanisms and expansive regulatory roles. However, currently, there is little research on how exosomal circRNAs are involved in the development of LC. Here, we demonstrated that circPVT1, a circRNA derived from the well-studied long noncoding RNA PVT1, is correlated with disease progression in LC and promotes angiogenesis both in vivo and in vitro. Mechanistically, circPVT1 is loaded into LC cell-secreted exosomes and taken up by vascular epithelium cells. By sponging miR-30c-5p, exosomal circPVT1 promotes Rap1b expression, which dramatically enhances vascular endothelial growth factor receptor 2 and the phosphatidylinositol 3-kinase (PI3K)/AKT pathway activation, ultimately resulting in the induction of angiogenesis. Furthermore, our xenograft models demonstrated that the combination of short hairpin RNA-circPVT1 and cetuximab showed high efficacy in inhibiting tumor growth and angiogenesis. Collectively, these findings uncover a novel mechanism of exosomal circRNA-mediated angiogenesis modulation and provide a preclinical rationale for testing this analogous combination in patients with LC.

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来源期刊
Carcinogenesis
Carcinogenesis 医学-肿瘤学
CiteScore
9.20
自引率
2.10%
发文量
95
审稿时长
1 months
期刊介绍: Carcinogenesis: Integrative Cancer Research is a multi-disciplinary journal that brings together all the varied aspects of research that will ultimately lead to the prevention of cancer in man. The journal publishes papers that warrant prompt publication in the areas of Biology, Genetics and Epigenetics (including the processes of promotion, progression, signal transduction, apoptosis, genomic instability, growth factors, cell and molecular biology, mutation, DNA repair, genetics, etc.), Cancer Biomarkers and Molecular Epidemiology (including genetic predisposition to cancer, and epidemiology), Inflammation, Microenvironment and Prevention (including molecular dosimetry, chemoprevention, nutrition and cancer, etc.), and Carcinogenesis (including oncogenes and tumor suppressor genes in carcinogenesis, therapy resistance of solid tumors, cancer mouse models, apoptosis and senescence, novel therapeutic targets and cancer drugs).
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