Regulation of Exosomal miR-320d/FAM49B Axis by Guanylate Binding Protein 5 Promotes Cell Growth and Tumor Progression in Oral Squamous Cell Carcinoma

IF 2.3 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine Pub Date : 2025-03-17 DOI:10.1111/jop.13624

Kai-Fang Hu, Chih-Wen Shu, Chun-Feng Chen, Cheng-Hsin Lee, Hsiang-Chien Kung, Yu-Hsiang Chou, Chun-Lin Chen, Pei-Feng Liu

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引用次数: 0

Abstract

Background

Guanylate binding protein 5 (GBP5) and exosomal miRNAs are involved in tumor progression. While several studies reveal the connection between GBP5 and exosomes for immune response and infection, this relationship in cancer, particularly in oral squamous cell carcinoma (OSCC), remains unexplored.

Methods

The exosomal miRNA extracted from the cells was analyzed using next-generation sequencing. Bioinformatic tools were used to predict exosomal miRNA target genes. OSCC cell growth was verified by colony formation, cell viability, and cell cycle analysis. The Cancer Genome Atlas database was used to inspect the prognosis of OSCC patients.

Results

Our results showed that OSCC cells treated with exosomes from GBP5-silenced OSCC cells reduced colony formation. Also, 56 differentially expressed exosomal miRNAs were found in GBP5-silenced OSCC cells compared to scrambled OSCC cells. Among them, exosomal miR-320d exhibited the highest negative correlation with GBP5 in OSCC patients. High GBP5/low miR-320d co-expression was linked to reduced disease-free survival (DFS) in patients with OSCC. Interestingly, the inhibitory effect of GBP5-silenced exosomes on OSCC cell growth was reversed by miR-320d inhibitors. Moreover, five miR-320d target genes were predicted, and only Family with Sequence Similarity 49, Member B (FAM49B) showed a negative correlation with miR-320d. A decreased level of FAM49B was found in OSCC cells treated with exosomes derived from GBP5-silenced OSCC cells, while the decreased level of FAM49B was reversed by miR-320d inhibitors. Silencing FAM49B and GBP5-silenced exosomes enhanced the cytotoxicity of paclitaxel. FAM49B was abundantly expressed in tumor tissues, and high FAM49B/low miR-320d and high GBP5/high FAM49B co-expression were linked to reduced DFS of OSCC patients.

Conclusion

Our study suggests that GBP5 downregulated exosomal miR-320d may trigger FAM49B expression and facilitate OSCC tumor growth and progression.

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鸟苷酸结合蛋白5调控外泌体miR-320d/FAM49B轴促进口腔鳞状细胞癌细胞生长和肿瘤进展

背景：鸟苷酸结合蛋白5 （GBP5）和外泌体miRNAs参与肿瘤进展。虽然一些研究揭示了GBP5与免疫反应和感染的外泌体之间的联系，但这种关系在癌症，特别是在口腔鳞状细胞癌（OSCC）中仍未被探索。方法：采用新一代测序技术对细胞外泌体miRNA进行分析。使用生物信息学工具预测外泌体miRNA靶基因。通过集落形成、细胞活力和细胞周期分析证实了OSCC细胞的生长。肿瘤基因组图谱数据库用于检查OSCC患者的预后。结果：我们的研究结果表明，用gbp5沉默的OSCC细胞外泌体处理OSCC细胞可以减少集落的形成。此外，与打乱的OSCC细胞相比，在gbp5沉默的OSCC细胞中发现了56个差异表达的外泌体mirna。其中，外泌体miR-320d与OSCC患者GBP5负相关最高。高GBP5/低miR-320d共表达与OSCC患者无病生存期（DFS）降低有关。有趣的是，gbp5沉默的外泌体对OSCC细胞生长的抑制作用被miR-320d抑制剂逆转。此外，我们预测了5个miR-320d靶基因，只有Family with Sequence Similarity 49， Member B （FAM49B）与miR-320d呈负相关。在使用来自gbp5沉默的OSCC细胞的外泌体处理的OSCC细胞中，发现FAM49B水平降低，而miR-320d抑制剂可以逆转FAM49B水平的降低。FAM49B和gbp5沉默外泌体增强了紫杉醇的细胞毒性。FAM49B在肿瘤组织中大量表达，高FAM49B/低miR-320d和高GBP5/高FAM49B共表达与OSCC患者DFS降低有关。结论：我们的研究提示GBP5下调外泌体miR-320d可能触发FAM49B的表达，促进OSCC肿瘤的生长和进展。

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

Journal of Oral Pathology & Medicine 医学-病理学

CiteScore

5.90

自引率

6.10%

发文量

121

审稿时长

4-8 weeks

期刊介绍： The aim of the Journal of Oral Pathology & Medicine is to publish manuscripts of high scientific quality representing original clinical, diagnostic or experimental work in oral pathology and oral medicine. Papers advancing the science or practice of these disciplines will be welcomed, especially those which bring new knowledge and observations from the application of techniques within the spheres of light and electron microscopy, tissue and organ culture, immunology, histochemistry and immunocytochemistry, microbiology, genetics and biochemistry.