• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

外泌体miR-3682-3p通过RAS-MEK1/2-ERK1/2通路靶向ANGPT1抑制肝细胞癌血管生成

Exosomal miR-3682-3p Suppresses Angiogenesis by Targeting ANGPT1 via the RAS-MEK1/2-ERK1/2 Pathway in Hepatocellular Carcinoma.

作者信息

Dong Shuang-Shuang, Dong Dan-Dan, Yang Zhang-Fu, Zhu Gui-Qi, Gao Dong-Mei, Chen Jie, Zhao Yan, Liu Bin-Bin

机构信息

Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

出版信息

Front Cell Dev Biol. 2021 Mar 29;9:633358. doi: 10.3389/fcell.2021.633358. eCollection 2021.

DOI:10.3389/fcell.2021.633358
PMID:33869178
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8044774/
Abstract

BACKGROUND

Angiogenesis is a crucial process in tumorigenesis and development. The role of exosomes derived from hepatocellular carcinoma (HCC) cells in angiogenesis has not been clearly elucidated.

METHODS AND RESULTS

Exosomes were isolated from HCC cell lines (HCCLM3, MHCC97L, and PLC/RFP/5) by ultracentrifugation and identified by nano transmission electron microscopy (TEM), NanoSight analysis and western blotting, respectively. and analyses showed that exosomes isolated from highly metastatic HCC cells enhanced the migration, invasion and tube formation of human umbilical vein endothelial cells (HUVECs) compared to exosomes derived from poorly metastatic HCC cells. In addition, microarray analysis of HCC-Exos was conducted to identify potential functional molecules, and miR-3682-3p expression was found to be significantly downregulated in exosomes isolated from highly metastatic HCC cells. By gain-of-function experiments, we found that HCC cells secreted exosomal miR-3682-3p, which negatively regulates angiopoietin-1 (ANGPT1), and this led to inhibition of RAS-MEK1/2-ERK1/2 signaling in endothelial cells and eventually impaired angiogenesis.

CONCLUSION

Our study elucidates that exosomal miR-3682-3p attenuates angiogenesis by targeting ANGPT1 through RAS-MEK1/2-ERK1/2 signaling and provides novel potential targets for liver cancer therapy.

摘要

背景

血管生成是肿瘤发生和发展中的关键过程。肝细胞癌（HCC）细胞来源的外泌体在血管生成中的作用尚未明确阐明。

方法与结果

通过超速离心从肝癌细胞系（HCCLM3、MHCC97L和PLC/RFP/5）中分离外泌体，并分别通过纳米透射电子显微镜（TEM）、纳米可视分析和蛋白质印迹法进行鉴定。 和 分析表明，与低转移肝癌细胞来源的外泌体相比，高转移肝癌细胞来源的外泌体增强了人脐静脉内皮细胞（HUVECs）的迁移、侵袭和管腔形成。此外，对肝癌外泌体进行微阵列分析以鉴定潜在的功能分子，发现高转移肝癌细胞来源的外泌体中miR-3682-3p表达显著下调。通过功能获得实验，我们发现肝癌细胞分泌外泌体miR-3682-3p，其负向调节血管生成素-1（ANGPT1），并导致内皮细胞中RAS-MEK1/2-ERK1/2信号传导受到抑制，最终损害血管生成。

结论

我们的研究阐明外泌体miR-3682-3p通过RAS-MEK1/2-ERK1/2信号传导靶向ANGPT1来减弱血管生成，并为肝癌治疗提供了新的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e86/8044774/cd7ec2e6dde3/fcell-09-633358-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e86/8044774/b48f9c7fd0ac/fcell-09-633358-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e86/8044774/9539893f767c/fcell-09-633358-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e86/8044774/28f003351efd/fcell-09-633358-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e86/8044774/60d5eaff2d64/fcell-09-633358-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e86/8044774/e1e23380c3f9/fcell-09-633358-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e86/8044774/d8251e6e6c6b/fcell-09-633358-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e86/8044774/cd7ec2e6dde3/fcell-09-633358-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e86/8044774/b48f9c7fd0ac/fcell-09-633358-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e86/8044774/9539893f767c/fcell-09-633358-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e86/8044774/28f003351efd/fcell-09-633358-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e86/8044774/60d5eaff2d64/fcell-09-633358-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e86/8044774/e1e23380c3f9/fcell-09-633358-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e86/8044774/d8251e6e6c6b/fcell-09-633358-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e86/8044774/cd7ec2e6dde3/fcell-09-633358-g007.jpg

相似文献

1
Exosomal miR-3682-3p Suppresses Angiogenesis by Targeting ANGPT1 via the RAS-MEK1/2-ERK1/2 Pathway in Hepatocellular Carcinoma.外泌体miR-3682-3p通过RAS-MEK1/2-ERK1/2通路靶向ANGPT1抑制肝细胞癌血管生成
Front Cell Dev Biol. 2021 Mar 29;9:633358. doi: 10.3389/fcell.2021.633358. eCollection 2021.
2
Golgi phosphoprotein 3 promotes angiogenesis and sorafenib resistance in hepatocellular carcinoma via upregulating exosomal miR-494-3p.高尔基体磷蛋白3通过上调外泌体miR-494-3p促进肝细胞癌血管生成和索拉非尼耐药。
Cancer Cell Int. 2022 Jan 24;22(1):35. doi: 10.1186/s12935-022-02462-9.
3
Exosomal miR-9-3p suppresses HBGF-5 expression and is a functional biomarker in hepatocellular carcinoma.外泌体miR-9-3p抑制肝素结合生长因子5（HBGF-5）的表达，是肝细胞癌的一种功能性生物标志物。
Minerva Med. 2018 Feb;109(1):15-23. doi: 10.23736/S0026-4806.17.05167-9. Epub 2017 Jul 27.
4
Angiopoietin-2 induces angiogenesis via exosomes in human hepatocellular carcinoma.血管生成素-2 通过外泌体诱导人肝癌血管生成。
Cell Commun Signal. 2020 Mar 17;18(1):46. doi: 10.1186/s12964-020-00535-8.
5
Blocking exosomal miRNA-153-3p derived from bone marrow mesenchymal stem cells ameliorates hypoxia-induced myocardial and microvascular damage by targeting the ANGPT1-mediated VEGF/PI3k/Akt/eNOS pathway.阻断源自骨髓间充质干细胞的外泌体miRNA-153-3p通过靶向ANGPT1介导的VEGF/PI3k/Akt/eNOS途径改善缺氧诱导的心肌和微血管损伤。
Cell Signal. 2021 Jan;77:109812. doi: 10.1016/j.cellsig.2020.109812. Epub 2020 Oct 24.
6
Hepatocellular carcinoma serum derived exosomal HIF-1α induces phosphoinositide-3 kinase/protein kinase B signaling to induce the angiogenesis and proliferation of HCC.肝癌血清来源的外泌体缺氧诱导因子-1α诱导磷脂酰肌醇-3激酶/蛋白激酶B信号传导，从而诱导肝癌的血管生成和增殖。
Transl Cancer Res. 2019 Aug;8(4):1550-1559. doi: 10.21037/tcr.2019.08.07.
7
Exosomal miR-451a Functions as a Tumor Suppressor in Hepatocellular Carcinoma by Targeting LPIN1.外泌体miR-451a通过靶向LPIN1在肝细胞癌中发挥肿瘤抑制作用。
Cell Physiol Biochem. 2019;53(1):19-35. doi: 10.33594/000000118.
8
Exosomes secreted by M2 macrophages promote cancer stemness of hepatocellular carcinoma via the miR-27a-3p/TXNIP pathways.M2 巨噬细胞分泌的外泌体通过 miR-27a-3p/TXNIP 通路促进肝癌干细胞特性。
Int Immunopharmacol. 2021 Dec;101(Pt A):107585. doi: 10.1016/j.intimp.2021.107585. Epub 2021 Sep 30.
9
Hepatocellular Carcinoma Cell-Secreted Exosomal MicroRNA-210 Promotes Angiogenesis In Vitro and In Vivo.肝癌细胞分泌的外泌体微小RNA-210在体内外均可促进血管生成。
Mol Ther Nucleic Acids. 2018 Jun 1;11:243-252. doi: 10.1016/j.omtn.2018.02.014. Epub 2018 Mar 6.
10
Glioma exosomal microRNA-148a-3p promotes tumor angiogenesis through activating the EGFR/MAPK signaling pathway via inhibiting ERRFI1.胶质瘤外泌体微小RNA-148a-3p通过抑制ERRFI1激活EGFR/MAPK信号通路促进肿瘤血管生成。
Cancer Cell Int. 2020 Oct 27;20:518. doi: 10.1186/s12935-020-01566-4. eCollection 2020.

引用本文的文献

1
Inhibiting Pyk2/Src expression by miR-23b-3p suppressed liver cancer stem cell function and hepatic carcinoma progression.通过miR-23b-3p抑制Pyk2/Src表达可抑制肝癌干细胞功能及肝癌进展。
Cancer Cell Int. 2025 Jun 7;25(1):205. doi: 10.1186/s12935-025-03841-8.
2
Immunosuppressive tumor microenvironment in the progression, metastasis, and therapy of hepatocellular carcinoma: from bench to bedside.免疫抑制性肿瘤微环境在肝细胞癌进展、转移及治疗中的作用：从实验台到临床应用
Exp Hematol Oncol. 2024 Aug 1;13(1):72. doi: 10.1186/s40164-024-00539-x.
3
Research progress of exosomes in the angiogenesis of digestive system tumour.

本文引用的文献

1
Lipotoxic Hepatocyte-Derived Exosomal MicroRNA 192-5p Activates Macrophages Through Rictor/Akt/Forkhead Box Transcription Factor O1 Signaling in Nonalcoholic Fatty Liver Disease.脂毒性肝细胞衍生的外泌体 microRNA-192-5p 通过 Rictor/Akt/Forkhead Box 转录因子 O1 信号通路激活非酒精性脂肪性肝病中的巨噬细胞。
Hepatology. 2020 Aug;72(2):454-469. doi: 10.1002/hep.31050. Epub 2020 May 16.
2
Targeting miRNAs by histone deacetylase inhibitors (HDACi): Rationalizing epigenetics-based therapies for breast cancer.组蛋白去乙酰化酶抑制剂（HDACi）靶向 microRNA：基于表观遗传学的乳腺癌治疗的合理化。
Pharmacol Ther. 2020 Feb;206:107437. doi: 10.1016/j.pharmthera.2019.107437. Epub 2019 Nov 9.
3
外泌体在消化系统肿瘤血管生成中的研究进展
Discov Oncol. 2024 Feb 11;15(1):33. doi: 10.1007/s12672-024-00879-4.
4
Celestial Insights: Unraveling the Role of miR-3682-3p in Hepatocellular Carcinoma.《天体洞察：解析miR-3682-3p在肝细胞癌中的作用》
Clin Transl Gastroenterol. 2024 Apr 1;15(4):e00690. doi: 10.14309/ctg.0000000000000690.
5
An Insight into the Arising Role of MicroRNAs in Hepatocellular Carcinoma: Future Diagnostic and Therapeutic Approaches.浅析 microRNAs 在肝细胞癌中的涌现角色：未来的诊断和治疗方法。
Int J Mol Sci. 2023 Apr 12;24(8):7168. doi: 10.3390/ijms24087168.
6
Non-coding RNAs in hepatocellular carcinoma: Insights into regulatory mechanisms, clinical significance, and therapeutic potential.非编码 RNA 在肝细胞癌中的作用：调控机制、临床意义及治疗潜能的深入探讨。
Front Immunol. 2022 Oct 10;13:985815. doi: 10.3389/fimmu.2022.985815. eCollection 2022.
7
miR-3682-3p directly targets FOXO3 and stimulates tumor stemness in hepatocellular carcinoma a positive feedback loop involving FOXO3/PI3K/AKT/c-Myc.miR-3682-3p直接靶向FOXO3并刺激肝细胞癌中的肿瘤干性，形成一个涉及FOXO3/PI3K/AKT/c-Myc的正反馈环。
World J Stem Cells. 2022 Jul 26;14(7):539-555. doi: 10.4252/wjsc.v14.i7.539.
8
Roles of small extracellular vesicles in the development, diagnosis and possible treatment strategies for hepatocellular carcinoma (Review).小细胞外囊泡在肝细胞癌的发展、诊断及可能的治疗策略中的作用（综述）。
Int J Oncol. 2022 Aug;61(2). doi: 10.3892/ijo.2022.5381. Epub 2022 Jun 8.
9
Identification of MAD2L1 as a Potential Biomarker in Hepatocellular Carcinoma via Comprehensive Bioinformatics Analysis.通过综合生物信息学分析鉴定 MAD2L1 为肝癌的潜在生物标志物。
Biomed Res Int. 2022 Jan 28;2022:9868022. doi: 10.1155/2022/9868022. eCollection 2022.
10
Role of Exosomes in Immune Microenvironment of Hepatocellular Carcinoma.外泌体在肝细胞癌免疫微环境中的作用
J Oncol. 2022 Jan 28;2022:2521025. doi: 10.1155/2022/2521025. eCollection 2022.
Elevated TRIP13 drives the AKT/mTOR pathway to induce the progression of hepatocellular carcinoma via interacting with ACTN4.
TRIP13 升高通过与 ACTN4 相互作用驱动 AKT/mTOR 通路诱导肝细胞癌的进展。
J Exp Clin Cancer Res. 2019 Sep 18;38(1):409. doi: 10.1186/s13046-019-1401-y.
4
Exosomes.外泌体。
Annu Rev Biochem. 2019 Jun 20;88:487-514. doi: 10.1146/annurev-biochem-013118-111902.
5
Cancer-derived exosomal miR-25-3p promotes pre-metastatic niche formation by inducing vascular permeability and angiogenesis.肿瘤来源的外泌体 miR-25-3p 通过诱导血管通透性和血管生成促进前转移龛形成。
Nat Commun. 2018 Dec 19;9(1):5395. doi: 10.1038/s41467-018-07810-w.
6
Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.全球癌症统计数据 2018：GLOBOCAN 对全球 185 个国家/地区 36 种癌症的发病率和死亡率的估计。
CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.
7
Hepatocellular Carcinoma Cell-Secreted Exosomal MicroRNA-210 Promotes Angiogenesis In Vitro and In Vivo.肝癌细胞分泌的外泌体微小RNA-210在体内外均可促进血管生成。
Mol Ther Nucleic Acids. 2018 Jun 1;11:243-252. doi: 10.1016/j.omtn.2018.02.014. Epub 2018 Mar 6.
8
Tumor-derived exosomes induce PD1 macrophage population in human gastric cancer that promotes disease progression.肿瘤来源的外泌体在人类胃癌中诱导产生促进疾病进展的PD1巨噬细胞群体。
Oncogenesis. 2018 May 25;7(5):41. doi: 10.1038/s41389-018-0049-3.
9
Hepatoma cell-secreted exosomal microRNA-103 increases vascular permeability and promotes metastasis by targeting junction proteins.肝癌细胞分泌的外泌体 microRNA-103 通过靶向连接蛋白增加血管通透性并促进转移。
Hepatology. 2018 Oct;68(4):1459-1475. doi: 10.1002/hep.29920. Epub 2018 Jul 25.
10
Tumor-derived exosomal miR-1247-3p induces cancer-associated fibroblast activation to foster lung metastasis of liver cancer.肿瘤来源的外泌体miR-1247-3p诱导癌症相关成纤维细胞活化以促进肝癌的肺转移。
Nat Commun. 2018 Jan 15;9(1):191. doi: 10.1038/s41467-017-02583-0.