AMPK in Chemoradiotherapy-Induced Oral Mucositis

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.13626

Junjie Jiang, Hao Xu, Mingyue Liu, Jiwei Guo, Jing Li, Jianwen Li, Hengtai Bi, Yousen Wang, Zhiliang Wang

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引用次数: 0

Abstract

Background

Oral mucositis (OM) is a prevalent adverse effect of radiotherapy and chemotherapy, significantly impacting cancer patients' well-being and potentially increasing mortality rates. Understanding OM's pathogenesis and identifying effective preventative and therapeutic agents are clinically crucial.

Methods

This study analyzed RNA-Seq data from the GEO database, focusing on OM samples post-radiotherapy and chemotherapy. Differential gene expression analysis between OM and non-OM groups, followed by gene ontology (GO) enrichment analysis of differentially expressed genes (DEGs), was conducted. LASSO regression identified five potential biomarkers, and CIBERSORT assessed immune infiltration in OM samples. Correlations between biomarkers and immune infiltration were explored, and the connectivity map (CMAP) screened potential therapeutic drugs. The top 10 drugs were validated through molecular docking.

Results

A total of 47 DEGs were identified, primarily involved in mitotic sister chromatid separation according to GO enrichment analysis. CIBERSORT analysis revealed significant changes in B cell naive and dendriform cells (DCs) resting content in the OM group. PRKAA2, encoding the AMP-activated protein kinase (AMPK) catalytic subunit, showed a negative correlation with DC resting content. Molecular docking from CMAP identified aloisine and teniposide as potential agents for OM induced by radiotherapy and chemotherapy.

Conclusion

AMPK emerges as a crucial regulator in OM post radiotherapy and chemotherapy, implicating sister chromatid separation, where DCs may play a pivotal role. Aloisine and Teniposide appear promising for OM prevention or treatment associated with these treatments.

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AMPK在放化疗诱导的口腔黏膜炎中的作用。

背景：口腔黏膜炎（OM）是放疗和化疗的普遍不良反应，严重影响癌症患者的健康，并可能增加死亡率。了解OM的发病机制和确定有效的预防和治疗药物在临床上至关重要。方法：本研究分析GEO数据库中的RNA-Seq数据，重点分析放疗和化疗后的OM样本。对OM组和非OM组进行差异基因表达分析，然后对差异表达基因（DEGs）进行基因本体（GO）富集分析。LASSO回归鉴定了5个潜在的生物标志物，CIBERSORT评估了OM样本中的免疫浸润。探讨生物标志物与免疫浸润之间的相关性，并通过连接图（CMAP）筛选潜在的治疗药物。通过分子对接验证前10名药物。结果：根据氧化石墨烯富集分析，共鉴定出47个deg，主要参与有丝分裂姐妹染色单体的分离。CIBERSORT分析显示，OM组B细胞初始和树突状细胞（dc）静息含量发生了显著变化。编码amp活化蛋白激酶（AMPK）催化亚基的PRKAA2与DC静息含量呈负相关。CMAP的分子对接发现，芦荟氨酸和天尼泊苷是放疗和化疗诱导OM的潜在药物。结论：AMPK是放疗和化疗后OM的重要调节因子，涉及姐妹染色单体分离，其中dc可能起关键作用。Aloisine和Teniposide似乎有希望预防或治疗与这些治疗相关的OM。

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.