由于慢性炎症反应，炎症性肠病（IBD）与结直肠癌（CRC）的发展密切相关。巨噬细胞在调节微环境以促进肿瘤进展方面发挥着关键作用。外泌体是巨噬细胞和肿瘤细胞之间通讯的关键调节剂。巨噬细胞衍生的外泌体在IBD相关CRC发展中的机制仍不清楚。使用荧光激活细胞分选仪（FACS）分离巨噬细胞。分别通过定量实时聚合酶链反应和蛋白质印迹分析检测外泌体和CRC细胞中的RNA和蛋白质表达。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物测定、BrdU 染色、Transwell 测定和球体形成测定评估 CRC 细胞发育。通过检测富含亮氨酸重复序列的G蛋白偶联受体5（LGR5）阳性CRC细胞的比例以及LGR5、CD133和CD44的表达来确定干性水平。使用荧光素酶报告基因测定和RNA免疫沉淀测定进行分子相互作用实验。采用体内异种移植肿瘤模型和免疫组织化学观察病理变化。来自IBD相关CRC组织的巨噬细胞来源的外泌体富含核旁斑组装转录本1（NEAT1），能够促进CRC的体外和干性进展和干性。体内。外泌体NEAT1可以海绵miR-34a-5p，导致CRC细胞中PEA15表达的恢复并促进CRC的发展。抑制外泌体中的 NEAT1 可以有效抑制 CRC 异种移植模型中的肿瘤生长。这些发现为巨噬细胞如何影响 CRC 发展提供了新的见解，并强调外泌体 NEAT1 作为 CRC 治疗的治疗靶点。© 作者 2024。出版者牛津大学出版社代表克罗恩病

Inflammatory bowel disease (IBD) is closely associated with the development of colorectal cancer (CRC) due to the chronic inflammatory response. Macrophages play critical roles in regulating the microenvironment to facilitate tumor progression. Exosomes are key modulators for the communication between macrophages and tumor cells. The mechanism of macrophage-derived exosomes in IBD-related CRC development remains unclear.The macrophages were isolated using fluorescence activating cell sorter (FACS). The RNA and protein expressions in exosomes and CRC cells were examined by quantitative real-time polymerase chain reaction and western blot assays, respectively. CRC cell development was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, BrdU staining, Transwell assay, and spheroid formation assay. The level of stemness was determined by detecting the proportion of leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5)-positive CRC cells and the expression of LGR5, CD133, and CD44. Molecular interaction experiments were done using luciferase reporter assay and RNA immunoprecipitation assay. Xenograft tumor model in vivo and immunohistochemistry were used to observe the pathological changes.Macrophage-derived exosomes from IBD-related CRC tissues were enriched with nuclear paraspeckle assembly transcript 1 (NEAT1) and able to promote the progression and stemness of CRC both in vitro and in vivo. The exosomal NEAT1 could sponge miR-34a-5p, leading to the restoration of PEA15 expression in CRC cells and promoting the development of CRC. Inhibition of NEAT1 in exosomes could effectivity inhibit the tumor growth in the CRC xenograft model.These findings provide novel insights into how macrophages affect CRC development and highlight exosomal NEAT1 as a therapeutic target for CRC treatment.© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.