ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1561081
This article is part of the Research TopicImmunometabolism in Immunological Tolerance and Regulation: Novel Mechanisms and Clinical InterventionsView all 7 articles
Running head: The miR-941/FOXN4/TGF-β feedback loop promotes LUAD
Provisionally accepted
Xiaojing Zhang
Xitiong Huang
Xianying ZhangLichang Lai
Baoyi ZhuPeibin Lin
Zhanfang KangDazhong YinDongbo Tian
Zisheng Chen*
Jun Gao*- Qingyuan People's Hospital, Qingyuan, China
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Background: Lung adenocarcinoma (LUAD) is a major subtype of lung cancer and one of the deadliest cancers in humans. Dysregulation of miRNA activity in tumor-associated neutrophils (TANs) in the tumor microenvironment plays an important role in the occurrence and development of LUAD. Method: In this study, the miReact algorithm was used to analyze the single-cell RNA sequencing data of LUAD samples to reveal the miRNA profile characteristics of TANs in LUAD patients. The function of miR-941 was investigated in vivo and in vitro. The target gene and underlying signaling pathway of miR-941 were predicted and validated with qPCR, luciferase assay, WB and ELISA assay. Results: The results indicated the crucial role of TANs, especially N2-TANs in LUAD and miR-941 activity was significantly upregulated in TANs of LUAD patients. MiR-941 overexpression promoted the proliferation, invasion, migration and anti-apoptosis of A549 and H1299. In vivo xenograft mouse model confirmed that miR-941 overexpression enhanced the growth of tumors formed by H1299 cells. Bioinformatics analysis showed that miR-941 targeted the tumor suppressor gene FOXN4, and we confirmed that FOXN4 overexpression could counteract the malignant effects of miR-941. In addition, miR-941 may drive LUAD progression through the FOXN4/TGF-β feedback signaling loop and participate in the N2-TAN. Conclusion: In summary, these findings reveal the key role of N2-TAN and the miR-941/FOXN4/TGF-β signaling loop in LUAD progression and provide potential therapeutic targets for future interventions.
Keywords: lung adenocarcinoma (LUAD), single-cell RNA sequencing (scRNA-seq), Tumor-associated neutrophils (TANs), miR-941, Foxn4, TGF-β
Received: 23 Jan 2025; Accepted: 31 Mar 2025.
Copyright: © 2025 Zhang, Huang, Zhang, Lai, Zhu, Lin, Kang, Yin, Tian, Chen and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zisheng Chen, Qingyuan People's Hospital, Qingyuan, China
Jun Gao, Qingyuan People's Hospital, Qingyuan, China
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