TAM‐Derived Exosomes Promote EMT by Upregulating lncRNA MIR4435‐2HG in Head and Neck Cancer

• Published in: Oral diseases Vol. 31; no. 4; pp. 1154 - 1164
• Main Authors: Liu, Junjiang, Mu, Jingtian, Liang, Zhi, Zhang, Yizhi, Hu, Tao, Wu, Fanglong, Zhou, Hongmei
• Format: Journal Article
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01.04.2025
• Subjects: Bioinformatics; Cell Line, Tumor; Cell Movement; Culture Media, Conditioned; Epithelial-Mesenchymal Transition - genetics; epithelial–mesenchymal transition; exosome; Exosomes; Exosomes - metabolism; Gene Expression Regulation, Neoplastic; Head & neck cancer; Head and neck carcinoma; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; head and neck squamous cell carcinoma; Humans; Macrophages; MicroRNAs - genetics; MicroRNAs - metabolism; MIR4435‐2HG; Nanoparticles; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - genetics; Squamous Cell Carcinoma of Head and Neck - metabolism; Squamous Cell Carcinoma of Head and Neck - pathology; Transmission electron microscopy; Tumor-Associated Macrophages - metabolism; tumor‐associated macrophages; Up-Regulation; Western blotting; Wound healing; epithelial–mesenchymal transition; tumor‐associated macrophages; MIR4435‐2HG; exosome; head and neck squamous cell carcinoma
• ISSN: 1354-523X; 1601-0825; 1601-0825
• DOI: 10.1111/odi.15212

ABSTRACT Objective This study aimed to investigate the impact of tumor‐associated macrophage (TAM)‐derived exosomes on epithelial–mesenchymal transition (EMT) in head and neck squamous cell carcinoma (HNSCC) and the underlying mechanisms involved. Subjects and Methods Exosomes were isolated and characterized using transmission electron microscopy, nanoparticle size analysis, and western blotting. The effect on EMT in HNSCC cells was assessed using wound healing, transwell invasion, and EMT marker assays. Bioinformatics analysis was conducted to predict key TAM‐related long noncoding RNAs and evaluate their relationship with EMT in HNSCC. Results We observed that treatment with TAM‐derived conditioned medium (CM) promoted EMT in HNSCC cells. Within the CM, we observed abundant exosomes that were taken up by HNSCC cells. Furthermore, TAM‐derived exosomes promoted EMT in HNSCC cells. Mechanistically, high MIR4435‐2HG expression levels were observed in TAM‐derived exosomes and in HNSCC cells after treatment with TAM‐derived exosomes. Notably, high MIR4435‐2HG expression levels may be closely related to molecules that promote EMT in HNSCC. Conclusions TAM‐derived exosomes promote EMT in HNSCC cells by upregulating MIR4435‐2HG expression, suggesting that MIR4435‐2HG is a candidate target for HNSCC therapy.