N2 neutrophils induce cell stemness reprogramming to promote gastric cancer progression via exosomal miRNAs

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2025-08-25 DOI:10.1016/j.cellsig.2025.112085

Haozhou Tang , Yuan Zhong , Jiayi Wang , Shuting Meng , Dan Yu , Baiyuan Fan , Xiaotong Dong , Maoye Wang , Min Fu , Yu Qian , Xiaoxin Zhang , Runbi Ji , Xu Zhang , Xinjian Fang , Jiahui Zhang

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引用次数: 0

Abstract

Exosomes mediate cellular communications and have a profound impact on cancer progression. N2 neutrophils, which are polarized by factors from cancers, extensively infiltrate into tumor tissues and promote cancer progression via distinct mechanisms. However, the role and underlying mechanism of exosomes derived from N2 neutrophils (N2-EXO) in cancer remain to be investigated. Herein, we reported that N2-EXO enhanced the proliferation and metastasis of gastric cancer (GC) cells by promoting their stemness. In addition, miR-223-3p and miR-425-5p, which were highly expressed in N2-EXO from GC patients, promoted cancer metastasis and reduced cancer sensitivity to oxaliplatin. The cancer-promoting effect of N2-EXO was abolished by the addition of miRNA inhibitor both in vitro and in vivo. Mechanically, miR-223-3p and miR-425-5p directly targeted FOXO3 and PTEN genes, respectively, which synergistically promoted GC progression by regulating PI3K/AKT signaling pathway. Taken together, our results reveal a novel mechanism by which N2-EXO promotes GC progression, providing new insights into the function of exosomes from N2 neutrophils in cancer.

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N2中性粒细胞诱导细胞干细胞重编程，通过外泌体mirna促进胃癌进展

外泌体介导细胞通讯并对癌症进展有深远的影响。N2中性粒细胞被肿瘤因子极化，广泛浸润到肿瘤组织中，通过不同的机制促进肿瘤进展。然而，来自N2中性粒细胞（N2- exo）的外泌体在癌症中的作用和潜在机制仍有待研究。本文报道N2-EXO通过促进胃癌细胞的干性来促进胃癌细胞的增殖和转移。此外，在胃癌患者的N2-EXO中高表达的miR-223-3p和miR-425-5p促进了癌症转移，降低了癌症对奥沙利铂的敏感性。在体外和体内均通过添加miRNA抑制剂来消除N2-EXO的促癌作用。机械上，miR-223-3p和miR-425-5p分别直接靶向FOXO3和PTEN基因，通过调节PI3K/AKT信号通路协同促进GC进展。综上所述，我们的研究结果揭示了N2- exo促进GC进展的新机制，为N2中性粒细胞外泌体在癌症中的功能提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.