• 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

TGF-β 介导线粒体 exosomal lnc-MMP2-2 通过促进 MMP2 表达来调节肺癌细胞向血管的迁移和侵袭。

TGF-β-mediated exosomal lnc-MMP2-2 regulates migration and invasion of lung cancer cells to the vasculature by promoting MMP2 expression.

机构信息

Clinical Laboratory, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China.

出版信息

Cancer Med. 2018 Oct;7(10):5118-5129. doi: 10.1002/cam4.1758. Epub 2018 Sep 6.

DOI:10.1002/cam4.1758
PMID:30256540
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6198203/
Abstract

Previous studies indicated that transforming growth factor (TGF)-β-mediated exosomal microRNAs (miRNAs) regulate the migration and invasion of lung cancer cells; however, whether and how TGF-β-mediated exosomal long noncoding (lnc) RNAs regulate migration and invasion of lung cancer cells remains unclear. Here, coculture experiments showed that TGF-β pretreatment increased the migration and invasion potential of lung cancer cells and TGF-β pretreated A549 cells increases vascular permeability. Furthermore, we found that TGF-β-mediated exosomes, as carriers of intercellular communication, regulated lung cancer invasion, and vascular permeability. Transcriptional analysis also revealed that lnc-MMP2-2 was highly enriched in TGF-β-mediated exosomes and might function by increasing the expression of matrix metalloproteinase (MMP)2 through its enhancer activity, with ectopic expression and silencing of lnc-MMP2-2 affecting lung cancer invasion and vascular permeability. Additionally, lnc-MMP2-2 and MMP2 expression was assessed semiquantitatively, and tissue-specific correlations between lnc-MMP2-2 and MMP2 expression were evaluated. These results suggested that exosomal lnc-MMP2-2 might regulate the migration and invasion of lung cancer cells into the vasculature by promoting MMP2 expression, suggesting this lncRNA as a novel therapeutic target and predictive marker of tumor metastasis in lung cancer.

摘要

先前的研究表明，转化生长因子 (TGF)-β 介导的细胞外体 microRNAs (miRNAs) 调节肺癌细胞的迁移和侵袭；然而，TGF-β 介导的细胞外体长非编码 (lnc)RNAs 是否以及如何调节肺癌细胞的迁移和侵袭尚不清楚。在这里，共培养实验表明，TGF-β 预处理增加了肺癌细胞的迁移和侵袭潜力，并且 TGF-β 预处理的 A549 细胞增加了血管通透性。此外，我们发现 TGF-β 介导的细胞外体作为细胞间通讯的载体，调节肺癌的侵袭和血管通透性。转录分析还表明，lnc-MMP2-2 在 TGF-β 介导的细胞外体中高度富集，可能通过其增强子活性增加基质金属蛋白酶 (MMP)2 的表达来发挥作用，外源性表达和沉默 lnc-MMP2-2 影响肺癌的侵袭和血管通透性。此外，还对半定量评估了 lnc-MMP2-2 和 MMP2 的表达，并评估了 lnc-MMP2-2 和 MMP2 表达之间的组织特异性相关性。这些结果表明，细胞外体 lnc-MMP2-2 可能通过促进 MMP2 表达来调节肺癌细胞向血管的迁移和侵袭，提示该 lncRNA 作为肺癌转移的新型治疗靶点和预测标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d4f/6198203/904f107f7282/CAM4-7-5118-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d4f/6198203/1131b85875b2/CAM4-7-5118-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d4f/6198203/8b794efafa54/CAM4-7-5118-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d4f/6198203/aab7cbce1138/CAM4-7-5118-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d4f/6198203/9e1b38b755d1/CAM4-7-5118-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d4f/6198203/2a5771078590/CAM4-7-5118-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d4f/6198203/5de2982965f3/CAM4-7-5118-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d4f/6198203/904f107f7282/CAM4-7-5118-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d4f/6198203/1131b85875b2/CAM4-7-5118-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d4f/6198203/8b794efafa54/CAM4-7-5118-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d4f/6198203/aab7cbce1138/CAM4-7-5118-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d4f/6198203/9e1b38b755d1/CAM4-7-5118-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d4f/6198203/2a5771078590/CAM4-7-5118-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d4f/6198203/5de2982965f3/CAM4-7-5118-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d4f/6198203/904f107f7282/CAM4-7-5118-g007.jpg

相似文献

1
TGF-β-mediated exosomal lnc-MMP2-2 regulates migration and invasion of lung cancer cells to the vasculature by promoting MMP2 expression.TGF-β 介导线粒体 exosomal lnc-MMP2-2 通过促进 MMP2 表达来调节肺癌细胞向血管的迁移和侵袭。
Cancer Med. 2018 Oct;7(10):5118-5129. doi: 10.1002/cam4.1758. Epub 2018 Sep 6.
2
TGF-β1-mediated exosomal lnc-MMP2-2 increases blood-brain barrier permeability via the miRNA-1207-5p/EPB41L5 axis to promote non-small cell lung cancer brain metastasis.TGF-β1 介导体细胞外囊泡 lnc-MMP2-2 通过 miRNA-1207-5p/EPB41L5 轴增加血脑屏障通透性，促进非小细胞肺癌脑转移。
Cell Death Dis. 2021 Jul 20;12(8):721. doi: 10.1038/s41419-021-04004-z.
3
Exosomal long noncoding RNA MLETA1 promotes tumor progression and metastasis by regulating the miR-186-5p/EGFR and miR-497-5p/IGF1R axes in non-small cell lung cancer.外泌体长链非编码 RNA MLETA1 通过调控非小细胞肺癌中 miR-186-5p/EGFR 和 miR-497-5p/IGF1R 轴促进肿瘤进展和转移。
J Exp Clin Cancer Res. 2023 Oct 26;42(1):283. doi: 10.1186/s13046-023-02859-y.
4
Long noncoding RNAs AC026904.1 is essential for TGF-β-induced migration and epithelial-mesenchymal transition through functioning as an enhancer of Slug in lung cancer cells.长链非编码 RNA AC026904.1 通过作为 Slug 的增强子在肺癌细胞中发挥作用，对于 TGF-β诱导的迁移和上皮-间充质转化是必不可少的。
Environ Toxicol. 2020 Sep;35(9):942-951. doi: 10.1002/tox.22930. Epub 2020 Apr 9.
5
Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts.肿瘤来源的外泌体 lncRNA-SOX2OT 通过靶向破骨细胞中的 miRNA-194-5p/RAC1 信号轴促进非小细胞肺癌骨转移。
Cell Death Dis. 2021 Jul 2;12(7):662. doi: 10.1038/s41419-021-03928-w.
6
Long non-coding RNA XIST promotes TGF-β-induced epithelial-mesenchymal transition by regulating miR-367/141-ZEB2 axis in non-small-cell lung cancer.长链非编码 RNA XIST 通过调控 miR-367/141-ZEB2 轴促进 TGF-β诱导的非小细胞肺癌上皮-间质转化。
Cancer Lett. 2018 Apr 1;418:185-195. doi: 10.1016/j.canlet.2018.01.036. Epub 2018 Jan 17.
7
Pigment epithelium-derived factor inhibits lung cancer migration and invasion by upregulating exosomal thrombospondin 1.色素上皮衍生因子通过上调外泌体血栓素 1 抑制肺癌迁移和侵袭。
Cancer Lett. 2019 Feb 1;442:287-298. doi: 10.1016/j.canlet.2018.10.031. Epub 2018 Nov 12.
8
MED28 and forkhead box M1 (FOXM1) mediate matrix metalloproteinase 2 (MMP2)-dependent cellular migration in human nonsmall cell lung cancer (NSCLC) cells.MED28 和叉头框蛋白 M1（FOXM1）介导人类非小细胞肺癌（NSCLC）细胞中基质金属蛋白酶 2（MMP2）依赖性细胞迁移。
J Cell Physiol. 2019 Jul;234(7):11265-11275. doi: 10.1002/jcp.27784. Epub 2018 Nov 29.
9
Tumor-derived exosomal lnc-Sox2ot promotes EMT and stemness by acting as a ceRNA in pancreatic ductal adenocarcinoma.肿瘤来源的外泌体 lnc-Sox2ot 通过作为 ceRNA 在胰腺导管腺癌中发挥作用促进 EMT 和干性。
Oncogene. 2018 Jul;37(28):3822-3838. doi: 10.1038/s41388-018-0237-9. Epub 2018 Apr 12.
10
Long noncoding RNA LINC01186, regulated by TGF-β/SMAD3, inhibits migration and invasion through Epithelial-Mesenchymal-Transition in lung cancer.由转化生长因子-β/信号转导和转录激活因子3（TGF-β/SMAD3）调控的长链非编码RNA LINC01186通过上皮-间质转化抑制肺癌的迁移和侵袭。
Gene. 2017 Apr 15;608:1-12. doi: 10.1016/j.gene.2017.01.023. Epub 2017 Jan 22.

引用本文的文献

1
Exosomal delivery of non-coding RNAs: a pathway to apoptosis regulation in lung cancer.外泌体介导的非编码RNA传递：肺癌细胞凋亡调控途径
Med Oncol. 2025 Jul 1;42(8):307. doi: 10.1007/s12032-025-02852-9.
2
Unveiling the power of exosomal non-coding RNAs: key drivers of lung cancer progression in the tumor microenvironment.揭示外泌体非编码RNA的力量：肿瘤微环境中肺癌进展的关键驱动因素
Med Oncol. 2025 Jul 1;42(8):308. doi: 10.1007/s12032-025-02791-5.
3
Diagnostic value of exosome-derived lncRNA PITPNA-AS1 in lung cancer.外泌体来源的长链非编码RNA PITPNA-AS1在肺癌中的诊断价值

本文引用的文献

1
SLC39A4 expression is associated with enhanced cell migration, cisplatin resistance, and poor survival in non-small cell lung cancer.SLC39A4 的表达与非小细胞肺癌中增强的细胞迁移、顺铂耐药和不良生存相关。
Sci Rep. 2017 Aug 3;7(1):7211. doi: 10.1038/s41598-017-07830-4.
2
The major thoracic vascular invasion of lung cancer.肺癌的主要胸段血管侵犯
Ann Med Surg (Lond). 2017 Jun 20;20:13-18. doi: 10.1016/j.amsu.2017.06.025. eCollection 2017 Aug.
3
LncRNA-PVT1 promotes pancreatic cancer cells proliferation and migration through acting as a molecular sponge to regulate miR-448.
Front Immunol. 2025 Apr 24;16:1539557. doi: 10.3389/fimmu.2025.1539557. eCollection 2025.
4
Functional tumor-derived exosomes in NSCLC progression and clinical implications.功能性肿瘤来源外泌体在非小细胞肺癌进展中的作用及临床意义
Front Pharmacol. 2025 Mar 19;16:1485661. doi: 10.3389/fphar.2025.1485661. eCollection 2025.
5
Molecular Underpinnings of Brain Metastases.脑转移瘤的分子基础
Int J Mol Sci. 2025 Mar 5;26(5):2307. doi: 10.3390/ijms26052307.
6
Exosomal long non-coding RNAs in lung cancer: A review.肺癌中的外泌体长链非编码RNA：综述
Medicine (Baltimore). 2024 Dec 20;103(51):e38492. doi: 10.1097/MD.0000000000038492.
7
A review of the complex interplay between chemoresistance and lncRNAs in lung cancer.肺癌中化疗耐药与长链非编码RNA之间复杂相互作用的综述
J Transl Med. 2024 Dec 5;22(1):1109. doi: 10.1186/s12967-024-05877-2.
8
Long non-coding RNAs in ferroptosis, pyroptosis and necroptosis: from functions to clinical implications in cancer therapy.铁死亡、焦亡和坏死性凋亡中的长链非编码RNA：从功能到癌症治疗中的临床意义
Front Oncol. 2024 Aug 29;14:1437698. doi: 10.3389/fonc.2024.1437698. eCollection 2024.
9
Tumor-associated exosomes in cancer progression and therapeutic targets.肿瘤相关外泌体在癌症进展及治疗靶点中的作用
MedComm (2020). 2024 Sep 7;5(9):e709. doi: 10.1002/mco2.709. eCollection 2024 Sep.
10
Harnessing exosomes as cancer biomarkers in clinical oncology.在临床肿瘤学中利用外泌体作为癌症生物标志物。
Cancer Cell Int. 2024 Aug 7;24(1):278. doi: 10.1186/s12935-024-03464-5.
长链非编码 RNA-PVT1 通过作为分子海绵调节 miR-448 促进胰腺癌细胞增殖和迁移。
J Cell Physiol. 2018 May;233(5):4044-4055. doi: 10.1002/jcp.26072. Epub 2017 Nov 30.
4
Overexpression of PAK1 Correlates with Aberrant Expression of EMT Markers and Poor Prognosis in Non-Small Cell Lung Cancer.PAK1的过表达与非小细胞肺癌中EMT标志物的异常表达及不良预后相关。
J Cancer. 2017 Jun 1;8(8):1484-1491. doi: 10.7150/jca.18553. eCollection 2017.
5
Transcriptional and posttranscriptional regulation of HOXA13 by lncRNA HOTTIP facilitates tumorigenesis and metastasis in esophageal squamous carcinoma cells.lncRNA HOTTIP对HOXA13的转录和转录后调控促进食管鳞状癌细胞的肿瘤发生和转移。
Oncogene. 2017 Sep 21;36(38):5392-5406. doi: 10.1038/onc.2017.133. Epub 2017 May 22.
6
Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis.外泌体递送的 EGFR 调节肝微环境促进胃癌肝转移。
Nat Commun. 2017 Apr 10;8:15016. doi: 10.1038/ncomms15016.
7
Emerging role of exosome-mediated intercellular communication in vascular remodeling.外泌体介导的细胞间通讯在血管重塑中的新作用。
Oncotarget. 2017 Apr 11;8(15):25700-25712. doi: 10.18632/oncotarget.14878.
8
Transcriptional Regulation of lncRNA Genes by Histone Modification in Alzheimer's Disease.阿尔茨海默病中组蛋白修饰对长链非编码RNA基因的转录调控
Biomed Res Int. 2016;2016:3164238. doi: 10.1155/2016/3164238. Epub 2016 Oct 16.
9
Exosome cargo reflects TGF-β1-mediated epithelial-to-mesenchymal transition (EMT) status in A549 human lung adenocarcinoma cells.外泌体货物反映了A549人肺腺癌细胞中转化生长因子-β1（TGF-β1）介导的上皮-间质转化（EMT）状态。
Biochem Biophys Res Commun. 2016 Sep 16;478(2):643-8. doi: 10.1016/j.bbrc.2016.07.124. Epub 2016 Aug 1.
10
The inhibition of calpains ameliorates vascular restenosis through MMP2/TGF-β1 pathway.钙蛋白酶抑制减轻通过 MMP2/TGF-β1 通路的血管再狭窄。
Sci Rep. 2016 Jul 25;6:29975. doi: 10.1038/srep29975.