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

Junjiang Liu¹, Jingtian Mu¹, Zhi Liang²

¹State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.

|December 9, 2024

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.

Keywords:

MIR4435‐2HG epithelial–mesenchymal transition exosome head and neck squamous cell carcinoma tumor‐associated macrophages

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Keywords:

MIR4435‐2HG epithelial–mesenchymal transition exosome head and neck squamous cell carcinoma tumor‐associated macrophages

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