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

IF 2.9 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Oral diseases Pub Date : 2024-12-09 DOI:10.1111/odi.15212

Junjiang Liu, Jingtian Mu, Zhi Liang, Yizhi Zhang, Tao Hu, Fanglong Wu, Hongmei Zhou

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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.

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tam衍生外泌体通过上调lncRNA MIR4435-2HG在头颈癌中促进EMT

目的：本研究旨在探讨肿瘤相关巨噬细胞（TAM）来源的外泌体对头颈部鳞状细胞癌（HNSCC）上皮-间质转化（EMT）的影响及其潜在机制。对象和方法：分离外泌体，并使用透射电子显微镜、纳米颗粒大小分析和免疫印迹法对其进行表征。通过伤口愈合、经井侵袭和EMT标记物测定来评估对HNSCC细胞EMT的影响。生物信息学分析预测了HNSCC中关键的tam相关长链非编码rna，并评估了它们与EMT的关系。结果：我们观察到tam衍生的条件培养基（CM）促进了HNSCC细胞的EMT。在CM中，我们观察到大量外泌体被HNSCC细胞占用。此外，tam衍生的外泌体促进了HNSCC细胞的EMT。在机制上，在tam来源的外泌体和用tam来源的外泌体处理后的HNSCC细胞中观察到高MIR4435-2HG表达水平。值得注意的是，MIR4435-2HG的高表达水平可能与HNSCC中促进EMT的分子密切相关。结论：tamm衍生的外泌体通过上调MIR4435-2HG的表达促进HNSCC细胞的EMT，提示MIR4435-2HG是HNSCC治疗的候选靶点。

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来源期刊

Oral diseases 医学-牙科与口腔外科

CiteScore

7.60

自引率

5.30%

发文量

325

审稿时长

4-8 weeks

期刊介绍： Oral Diseases is a multidisciplinary and international journal with a focus on head and neck disorders, edited by leaders in the field, Professor Giovanni Lodi (Editor-in-Chief, Milan, Italy), Professor Stefano Petti (Deputy Editor, Rome, Italy) and Associate Professor Gulshan Sunavala-Dossabhoy (Deputy Editor, Shreveport, LA, USA). The journal is pre-eminent in oral medicine. Oral Diseases specifically strives to link often-isolated areas of dentistry and medicine through broad-based scholarship that includes well-designed and controlled clinical research, analytical epidemiology, and the translation of basic science in pre-clinical studies. The journal typically publishes articles relevant to many related medical specialties including especially dermatology, gastroenterology, hematology, immunology, infectious diseases, neuropsychiatry, oncology and otolaryngology. The essential requirement is that all submitted research is hypothesis-driven, with significant positive and negative results both welcomed. Equal publication emphasis is placed on etiology, pathogenesis, diagnosis, prevention and treatment.

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