M2 macrophage-derived extracellular vesicles augment immune evasion and development of colorectal cancer via a circRNA_CCDC66/microRNA-342-3p/metadherin axis.

IF 1.7 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Cytotechnology Pub Date : 2023-08-01 Epub Date: 2023-04-19 DOI:10.1007/s10616-023-00577-z

Linfeng Fan, Guofeng Xu, Xiangfu Zeng

{"title":"M2 macrophage-derived extracellular vesicles augment immune evasion and development of colorectal cancer via a circRNA_CCDC66/microRNA-342-3p/metadherin axis.","authors":"Linfeng Fan, Guofeng Xu, Xiangfu Zeng","doi":"10.1007/s10616-023-00577-z","DOIUrl":null,"url":null,"abstract":"The M2 macrophages are major components in the tumor microenvironment and are closely linked to immune suppression and tumor metastasis. This work focuses on how M2 macrophage-derived extracellular vesicles (EVs) affect colorectal cancer (CRC) progression. THP-1 monocytes were induced to differentiate to M0 or M2 macrophages, and the macrophage-derived EVs (M0-EVs and M2-EVs, respectively) were collected and identified. The M2-EVs stimulation augmented proliferation, mobility, and the in vivo tumorigenic activity of CRC cells. Circular RNA_CCDC66 (circ_CCDC66) was highly enriched in M2-EVs and could be delivered into CRC cells. The RNA pull-down and luciferase assays showed that circ_CCDC66 could competitively bind to microRNA (miR)-342-3p, therefore restoring the expression of metadherin (MTDH) mRNA, a target transcript of miR-342-3p. Suppression of circ_CCDC66 in the M2-EVs or specific knockdown of MTDH in CRC significantly blocked the growth and mobility of CRC cells. However, miR-342-3p inhibition restored the malignant phenotype of cancer cells. Moreover, the MTDH knockdown was found to increase the cytotoxicity of CD8+ T and reduce the protein level of the immune checkpoint PDL1 in CRC cells. In summary, this study reveals that the M2-EVs augment immune evasion and development of CRC by delivering circ_CCDC66 and restoring the MTDH level.","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"75 4","pages":"293-308"},"PeriodicalIF":1.7000,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10299985/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cytotechnology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s10616-023-00577-z","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/4/19 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

The M2 macrophages are major components in the tumor microenvironment and are closely linked to immune suppression and tumor metastasis. This work focuses on how M2 macrophage-derived extracellular vesicles (EVs) affect colorectal cancer (CRC) progression. THP-1 monocytes were induced to differentiate to M0 or M2 macrophages, and the macrophage-derived EVs (M0-EVs and M2-EVs, respectively) were collected and identified. The M2-EVs stimulation augmented proliferation, mobility, and the in vivo tumorigenic activity of CRC cells. Circular RNA_CCDC66 (circ_CCDC66) was highly enriched in M2-EVs and could be delivered into CRC cells. The RNA pull-down and luciferase assays showed that circ_CCDC66 could competitively bind to microRNA (miR)-342-3p, therefore restoring the expression of metadherin (MTDH) mRNA, a target transcript of miR-342-3p. Suppression of circ_CCDC66 in the M2-EVs or specific knockdown of MTDH in CRC significantly blocked the growth and mobility of CRC cells. However, miR-342-3p inhibition restored the malignant phenotype of cancer cells. Moreover, the MTDH knockdown was found to increase the cytotoxicity of CD8⁺ T and reduce the protein level of the immune checkpoint PDL1 in CRC cells. In summary, this study reveals that the M2-EVs augment immune evasion and development of CRC by delivering circ_CCDC66 and restoring the MTDH level.

Abstract Image

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

M2巨噬细胞衍生的细胞外囊泡通过circRNA_CCDC66/microRNA-342-3p/metadherin轴增强免疫逃避和结直肠癌的发展。

M2 巨噬细胞是肿瘤微环境的主要组成部分，与免疫抑制和肿瘤转移密切相关。这项研究的重点是 M2 巨噬细胞衍生的胞外囊泡 (EV) 如何影响结直肠癌（CRC）的进展。研究人员诱导THP-1单核细胞分化为M0或M2巨噬细胞，收集并鉴定巨噬细胞衍生的EVs（分别为M0-EVs和M2-EVs）。M2-EVs刺激增强了CRC细胞的增殖、流动性和体内致瘤活性。环状RNA_CCDC66（circ_CCDC66）在M2-EVs中高度富集，并能被传递到CRC细胞中。RNA pull-down和荧光素酶实验表明，circ_CCDC66能与microRNA (miR)-342-3p竞争性结合，从而恢复miR-342-3p的靶转录本--偏球蛋白（MTDH）mRNA的表达。抑制 M2-EVs 中的 circ_CCDC66 或特异性敲除 CRC 中的 MTDH 能显著阻止 CRC 细胞的生长和移动。然而，抑制 miR-342-3p 能恢复癌细胞的恶性表型。此外，研究还发现 MTDH 基因敲除可增加 CD8+ T 的细胞毒性，并降低 CRC 细胞中免疫检查点 PDL1 的蛋白水平。总之，这项研究揭示了M2-EV通过递送circ_CCDC66和恢复MTDH水平来增强免疫逃避和CRC的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Cytotechnology 生物-生物工程与应用微生物

CiteScore

4.10

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The scope of the Journal includes: 1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products. 2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools. 3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research. 4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy. 5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.