Bioinformatics and In Vitro/In Vivo Experiments Identify MAD2L1 as an m6A-Associated Biomarker Promoting Oral Squamous Cell Carcinoma Progression

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

Journal of Oral Pathology & Medicine Pub Date : 2026-03-05 Epub Date: 2025-11-30 DOI:10.1111/jop.70096

Jilun Liu, Yongle Qiu, Song Li, Xin Zhang, Xiaojing Zhang, Jiahong Zhao

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引用次数: 0

Abstract

Background

Oral squamous cell carcinoma (OSCC) is a common malignant tumor of the head and neck, and its therapeutic efficacy critically depends on the identification of reliable biomarkers. This study investigates the interplay between m6A methylation-related biomarkers and OSCC progression biomarkers, aiming to enhance the understanding of pathogenic mechanisms and facilitate personalized treatment strategies.

Methods

Based on multi-dimensional bioinformatics analyses—including differential expression, enrichment, prognostic modeling, and immune infiltration analyses—of GEO and TCGA datasets, potential biomarkers that promote malignant progression in OSCC and their association with m6A-related molecules were identified. The effect of MAD2L1 on OSCC in vitro was assessed using CCK-8, RT-qPCR, colony formation, wound healing, and TUNEL assays, while Western blotting was employed to explore the underlying mechanisms by which MAD2L1 influences OSCC progression. Additionally, RT-qPCR was used to examine the impact of MAD2L1 on m6A-related biomarkers. Finally, a xenograft tumor model was utilized to evaluate the effect of MAD2L1 on tumor growth in vivo.

Results

Our findings demonstrate that MAD2L1 serves as a biomarker associated with the progression of oral squamous cell carcinoma (OSCC). Specifically, MAD2L1 expression was significantly upregulated in OSCC patients and positively correlated with increasing histopathological grade. Elevated MAD2L1 expression was linked to poor prognosis in OSCC patients and enabled the construction of an effective prognostic model. Furthermore, MAD2L1 expression showed significant positive correlations with multiple m6A-related biomarkers. Knockdown of MAD2L1 reduced the mRNA expression of THDC1, WTAP, and RBMX. In addition, MAD2L1 expression was significantly associated with tumor microenvironment (TME) dysregulation. Finally, both in vitro and in vivo experiments confirmed that MAD2L1 knockdown markedly suppressed OSCC cell growth.

Conclusion

Collectively, our study identifies MAD2L1 as a promising oncogenic biomarker and therapeutic target in OSCC, whose upregulation drives tumor progression, impairs patient prognosis, and disrupts m6A modification.

查看原文本刊更多论文

生物信息学和体外/体内实验鉴定MAD2L1是促进口腔鳞状细胞癌进展的m6a相关生物标志物。

背景：口腔鳞状细胞癌（Oral squamous cell carcinoma， OSCC）是一种常见的头颈部恶性肿瘤，其治疗效果关键取决于确定可靠的生物标志物。本研究探讨m6A甲基化相关生物标志物与OSCC进展生物标志物之间的相互作用，旨在增强对发病机制的理解，促进个性化治疗策略的制定。方法：基于GEO和TCGA数据集的多维生物信息学分析（包括差异表达、富集、预后建模和免疫浸润分析），鉴定出促进OSCC恶性进展的潜在生物标志物及其与m6a相关分子的关联。通过CCK-8、RT-qPCR、菌落形成、伤口愈合和TUNEL检测来评估MAD2L1对体外OSCC的影响，同时采用Western blotting来探索MAD2L1影响OSCC进展的潜在机制。此外，RT-qPCR用于检测MAD2L1对m6a相关生物标志物的影响。最后，利用异种移植肿瘤模型来评估MAD2L1对肿瘤体内生长的影响。结果：我们的研究结果表明，MAD2L1是与口腔鳞状细胞癌（OSCC）进展相关的生物标志物。具体而言，MAD2L1表达在OSCC患者中显著上调，并与组织病理分级的增加正相关。升高的MAD2L1表达与OSCC患者的不良预后有关，并有助于构建有效的预后模型。此外，MAD2L1的表达与多种m6a相关的生物标志物呈显著正相关。敲低MAD2L1可降低THDC1、WTAP和RBMX的mRNA表达。此外，MAD2L1表达与肿瘤微环境（TME）失调显著相关。最后，体外和体内实验均证实，MAD2L1敲低可显著抑制OSCC细胞的生长。结论：总的来说，我们的研究确定了MAD2L1是一个有希望的癌性生物标志物和OSCC的治疗靶点，其上调驱动肿瘤进展，损害患者预后，并破坏m6A修饰。

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.