• 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

M2 巨噬细胞衍生的细胞外囊泡介导的 miR-186-5p 转移通过靶向 DLC1 促进结肠癌进展。

M2 Macrophage Derived Extracellular Vesicle-Mediated Transfer of MiR-186-5p Promotes Colon Cancer Progression by Targeting DLC1.

机构信息

Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, P. R. China.

出版信息

Int J Biol Sci. 2022 Feb 7;18(4):1663-1676. doi: 10.7150/ijbs.69405. eCollection 2022.

DOI:10.7150/ijbs.69405
PMID:35280693
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8898350/
Abstract

Colon cancer (CC) is one of the most common malignances in digestive tract. M2-polarized macrophages within the tumor microenvironment could facilitate CC cell growth by transferring molecules via extracellular vesicles, but the mechanisms are not fully elucidated. The current study aims to identify the possible effectors in M2 macrophage-derived extracellular vesicles (M2-EVs) and reveal related molecular mechanisms. In our study, we validated the promotion effects of M2-EVs on the proliferation and motility of CC cells, which was found to be dependent on the EVs enclosed molecules by a mild EVs digestion assay. Then we found that miR-186-5p was enriched in M2-EVs and was responsible for the tumor promoting functions of M2-EVs. Furthermore, mechanism investigation revealed M2-EVs transferring miR-186-5p inhibited DLC1 expression by targeting its 3'UTR, and restored DLC1 successfully neutralized the tumor-promoting effects of M2-EVs transferring miR-186-5p via inhibiting the β-catenin pathway. Our study revealed that M2-EVs facilitates the growth and motility of CC cells by delivering the enclosed miR-186-5p, which directly targets DLC1 mRNAs and facilitates their degradation, which could provide a potential biomarker and therapeutic target for CC.

摘要

结肠癌（CC）是消化道最常见的恶性肿瘤之一。肿瘤微环境中的 M2 极化巨噬细胞可以通过细胞外囊泡转移分子来促进 CC 细胞的生长，但具体机制尚不完全清楚。本研究旨在鉴定 M2 巨噬细胞衍生的细胞外囊泡（M2-EVs）中的可能效应物，并揭示相关的分子机制。在我们的研究中，我们验证了 M2-EVs 对 CC 细胞增殖和迁移的促进作用，发现这一作用依赖于 EVs 包裹的分子，通过温和的 EVs 消化实验可以发现这一点。然后我们发现 miR-186-5p 在 M2-EVs 中富集，并负责 M2-EVs 的肿瘤促进功能。此外，机制研究表明 M2-EVs 转移的 miR-186-5p 通过靶向其 3'UTR 抑制 DLC1 表达，并且恢复 DLC1 成功中和了 M2-EVs 转移 miR-186-5p 通过抑制 β-连环蛋白途径的促肿瘤作用。我们的研究表明，M2-EVs 通过递送内含的 miR-186-5p 促进 CC 细胞的生长和迁移，该 miR-186-5p 直接靶向 DLC1 mRNAs 并促进其降解，这可为 CC 提供一个潜在的生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bc8/8898350/946e590f0d7b/ijbsv18p1663g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bc8/8898350/18896b735bb7/ijbsv18p1663g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bc8/8898350/7394d9e27043/ijbsv18p1663g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bc8/8898350/bfb23cbcc8ed/ijbsv18p1663g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bc8/8898350/e34f5c435890/ijbsv18p1663g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bc8/8898350/93cc9bb6dc97/ijbsv18p1663g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bc8/8898350/fc83cbcf742c/ijbsv18p1663g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bc8/8898350/946e590f0d7b/ijbsv18p1663g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bc8/8898350/18896b735bb7/ijbsv18p1663g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bc8/8898350/7394d9e27043/ijbsv18p1663g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bc8/8898350/bfb23cbcc8ed/ijbsv18p1663g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bc8/8898350/e34f5c435890/ijbsv18p1663g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bc8/8898350/93cc9bb6dc97/ijbsv18p1663g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bc8/8898350/fc83cbcf742c/ijbsv18p1663g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bc8/8898350/946e590f0d7b/ijbsv18p1663g007.jpg

相似文献

1
M2 Macrophage Derived Extracellular Vesicle-Mediated Transfer of MiR-186-5p Promotes Colon Cancer Progression by Targeting DLC1.M2 巨噬细胞衍生的细胞外囊泡介导的 miR-186-5p 转移通过靶向 DLC1 促进结肠癌进展。
Int J Biol Sci. 2022 Feb 7;18(4):1663-1676. doi: 10.7150/ijbs.69405. eCollection 2022.
2
Extracellular vesicle-packaged miR-181c-5p from epithelial ovarian cancer cells promotes M2 polarization of tumor-associated macrophages via the KAT2B/HOXA10 axis.上皮性卵巢癌细胞来源的细胞外囊泡包裹的 miR-181c-5p 通过 KAT2B/HOXA10 轴促进肿瘤相关巨噬细胞向 M2 极化。
J Gene Med. 2022 Oct;24(10):e3446. doi: 10.1002/jgm.3446. Epub 2022 Sep 19.
3
microRNA-15b-5p encapsulated by M2 macrophage-derived extracellular vesicles promotes gastric cancer metastasis by targeting BRMS1 and suppressing DAPK1 transcription.M2 巨噬细胞来源的细胞外囊泡包裹的 microRNA-15b-5p 通过靶向 BRMS1 和抑制 DAPK1 转录促进胃癌转移。
J Exp Clin Cancer Res. 2022 Apr 22;41(1):152. doi: 10.1186/s13046-022-02356-8.
4
microRNA-21-5p from M2 macrophage-derived extracellular vesicles promotes the differentiation and activity of pancreatic cancer stem cells by mediating KLF3.M2 巨噬细胞来源的细胞外囊泡中的 microRNA-21-5p 通过介导 KLF3 促进胰腺癌干细胞的分化和活性。
Cell Biol Toxicol. 2022 Aug;38(4):577-590. doi: 10.1007/s10565-021-09597-x. Epub 2021 Mar 17.
5
miR-365 secreted from M2 Macrophage-derived extracellular vesicles promotes pancreatic ductal adenocarcinoma progression through the BTG2/FAK/AKT axis.M2 巨噬细胞来源的细胞外囊泡分泌的 miR-365 通过 BTG2/FAK/AKT 轴促进胰腺导管腺癌的进展。
J Cell Mol Med. 2021 May;25(10):4671-4683. doi: 10.1111/jcmm.16405. Epub 2021 Apr 3.
6
Hypoxic glioma-derived extracellular vesicles harboring MicroRNA-10b-5p enhance M2 polarization of macrophages to promote the development of glioma.缺氧胶质瘤衍生的细胞外囊泡携带 microRNA-10b-5p 增强巨噬细胞 M2 极化，促进胶质瘤的发展。
CNS Neurosci Ther. 2022 Nov;28(11):1733-1747. doi: 10.1111/cns.13905. Epub 2022 Sep 2.
7
Mesenchymal stem cell-derived extracellular vesicles prevent glioma by blocking M2 polarization of macrophages through a miR-744-5p/TGFB1-dependent mechanism.间质干细胞衍生的细胞外囊泡通过 miR-744-5p/TGFB1 依赖机制阻止巨噬细胞 M2 极化从而抑制神经胶质瘤。
Cell Biol Toxicol. 2022 Aug;38(4):649-665. doi: 10.1007/s10565-021-09652-7. Epub 2022 Jan 3.
8
Pancreatic cancer cell-derived microRNA-155-5p-containing extracellular vesicles promote immune evasion by triggering EHF-dependent activation of Akt/NF-κB signaling pathway.胰腺癌细胞衍生的含微小RNA-155-5p的细胞外囊泡通过触发Akt/NF-κB信号通路的EHF依赖性激活来促进免疫逃逸。
Int Immunopharmacol. 2021 Nov;100:107990. doi: 10.1016/j.intimp.2021.107990. Epub 2021 Sep 3.
9
miR-143-3p shuttled by M2 macrophage-derived extracellular vesicles induces progression of colorectal cancer through a ZC3H12A/C/EBPβ axis-dependent mechanism.M2 巨噬细胞来源的细胞外囊泡转运的 miR-143-3p 通过 ZC3H12A/C/EBPβ 轴依赖性机制诱导结直肠癌的进展。
Int Immunopharmacol. 2023 Jun;119:110137. doi: 10.1016/j.intimp.2023.110137. Epub 2023 Apr 29.
10
Roles of hypoxic environment and M2 macrophage-derived extracellular vesicles on the progression of non-small cell lung cancer.缺氧微环境及 M2 巨噬细胞衍生细胞外囊泡在非小细胞肺癌进展中的作用。
BMC Pulm Med. 2023 Jul 3;23(1):239. doi: 10.1186/s12890-023-02468-7.

引用本文的文献

1
Tumor-associated macrophages in colon cancer immunotherapy: mechanisms, natural product interventions, and microenvironment remodeling.结肠癌免疫治疗中的肿瘤相关巨噬细胞：作用机制、天然产物干预及微环境重塑
Front Immunol. 2025 Aug 12;16:1642091. doi: 10.3389/fimmu.2025.1642091. eCollection 2025.
2
The dual effects of macrophage-derived extracellular vesicles on tumor cell behavior: mechanisms and clinical potential.巨噬细胞衍生的细胞外囊泡对肿瘤细胞行为的双重影响：机制与临床潜力
Front Oncol. 2025 May 23;15:1586083. doi: 10.3389/fonc.2025.1586083. eCollection 2025.
3
Prospect of extracellular vesicles in tumor immunotherapy.

本文引用的文献

1
M2 macrophage-derived exosomal microRNA-155-5p promotes the immune escape of colon cancer by downregulating ZC3H12B.M2巨噬细胞衍生的外泌体微小RNA-155-5p通过下调ZC3H12B促进结肠癌的免疫逃逸。
Mol Ther Oncolytics. 2021 Feb 6;20:484-498. doi: 10.1016/j.omto.2021.02.005. eCollection 2021 Mar 26.
2
Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.《全球癌症统计数据 2020：全球 185 个国家和地区 36 种癌症的发病率和死亡率估计》。
CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.
3
Angiogenesis is promoted by exosomal DPP4 derived from 5-fluorouracil-resistant colon cancer cells.
细胞外囊泡在肿瘤免疫治疗中的前景。
Front Immunol. 2025 Feb 26;16:1525052. doi: 10.3389/fimmu.2025.1525052. eCollection 2025.
4
Systemic immune profiling analysis identifying M2-TAM related genes predicted colon cancer prognosis and chemotherapy responses.系统性免疫谱分析鉴定出与M2型肿瘤相关巨噬细胞（M2-TAM）相关的基因，这些基因可预测结肠癌的预后和化疗反应。
Medicine (Baltimore). 2024 Dec 27;103(52):e40979. doi: 10.1097/MD.0000000000040979.
5
Macrophage-derived extracellular vesicles as new players in chronic non-communicable diseases.巨噬细胞衍生的细胞外囊泡在慢性非传染性疾病中扮演新角色。
Front Immunol. 2025 Jan 17;15:1479330. doi: 10.3389/fimmu.2024.1479330. eCollection 2024.
6
Apoptotic breast cancer cells after chemotherapy induce pro-tumour extracellular vesicles via LAP-competent macrophages.化疗后的凋亡乳腺癌细胞通过具有LAP活性的巨噬细胞诱导促肿瘤细胞外囊泡。
Redox Biol. 2025 Mar;80:103485. doi: 10.1016/j.redox.2024.103485. Epub 2024 Dec 28.
7
Extracellular vesicles and macrophages in tumor microenvironment: Impact on cervical cancer.肿瘤微环境中的细胞外囊泡与巨噬细胞：对宫颈癌的影响
Heliyon. 2024 Jul 26;10(15):e35063. doi: 10.1016/j.heliyon.2024.e35063. eCollection 2024 Aug 15.
8
The role of innate immune cells in the colorectal cancer tumor microenvironment and advances in anti-tumor therapy research.固有免疫细胞在结直肠癌肿瘤微环境中的作用及抗肿瘤治疗研究进展。
Front Immunol. 2024 Jul 19;15:1407449. doi: 10.3389/fimmu.2024.1407449. eCollection 2024.
9
The multifaceted role of extracellular vesicles (EVs) in colorectal cancer: metastasis, immune suppression, therapy resistance, and autophagy crosstalk.细胞外囊泡（EVs）在结直肠癌中的多效性作用：转移、免疫抑制、治疗抵抗和自噬串扰。
J Transl Med. 2024 May 13;22(1):452. doi: 10.1186/s12967-024-05267-8.
10
Key role of exosomes derived from M2 macrophages in maintaining cancer cell stemness (Review).外泌体在维持肿瘤细胞干性中的关键作用（综述）。
Int J Oncol. 2023 Nov;63(5). doi: 10.3892/ijo.2023.5574. Epub 2023 Sep 15.
外泌体 DPP4 促进血管生成，该 DPP4 源自 5-氟尿嘧啶耐药的结肠癌细胞。
Cancer Lett. 2021 Jan 28;497:190-201. doi: 10.1016/j.canlet.2020.10.009. Epub 2020 Oct 9.
4
miR-221-3p promotes hepatocellular carcinogenesis by downregulating O6-methylguanine-DNA methyltransferase.miR-221-3p 通过下调 O6-甲基鸟嘌呤-DNA 甲基转移酶促进肝癌发生。
Cancer Biol Ther. 2020 Oct 2;21(10):915-926. doi: 10.1080/15384047.2020.1806642. Epub 2020 Oct 6.
5
Exosomal Sonic Hedgehog derived from cancer-associated fibroblasts promotes proliferation and migration of esophageal squamous cell carcinoma.源自癌症相关成纤维细胞的外泌体音猬因子促进食管鳞状细胞癌的增殖和迁移。
Cancer Med. 2020 Apr;9(7):2500-2513. doi: 10.1002/cam4.2873. Epub 2020 Feb 7.
6
The Two Faces of Tumor-Associated Macrophages and Their Clinical Significance in Colorectal Cancer.肿瘤相关巨噬细胞的两面性及其在结直肠癌中的临床意义。
Front Immunol. 2019 Aug 20;10:1875. doi: 10.3389/fimmu.2019.01875. eCollection 2019.
7
Evaluation of circulating small extracellular vesicles derived miRNAs as biomarkers of early colon cancer: a comparison with plasma total miRNAs.评估循环小细胞外囊泡衍生的miRNA作为早期结肠癌生物标志物：与血浆总miRNA的比较
J Extracell Vesicles. 2019 Jul 22;8(1):1643670. doi: 10.1080/20013078.2019.1643670. eCollection 2019.
8
Macrophages and Metabolism in the Tumor Microenvironment.肿瘤微环境中的巨噬细胞和代谢
Cell Metab. 2019 Jul 2;30(1):36-50. doi: 10.1016/j.cmet.2019.06.001.
9
miR‑221‑3p promotes the cell growth of non‑small cell lung cancer by targeting p27.miR-221-3p 通过靶向 p27 促进非小细胞肺癌细胞的生长。
Mol Med Rep. 2019 Jul;20(1):604-612. doi: 10.3892/mmr.2019.10291. Epub 2019 May 23.
10
Exosome-mediated communication in the tumor microenvironment contributes to hepatocellular carcinoma development and progression.外泌体介导的肿瘤微环境通讯促进肝癌的发生和发展。
J Hematol Oncol. 2019 May 29;12(1):53. doi: 10.1186/s13045-019-0739-0.