MAGI2-AS3 hypermethylated in promoter region promotes migration and invasion of head and neck squamous cell carcinoma via miRNA-31-5p/AR axis

IF 5 2区 医学 Q2 Medicine Translational Oncology Pub Date : 2025-02-01 Epub Date: 2024-12-07 DOI:10.1016/j.tranon.2024.102223
Kai Yue , Ting Zhang , Huanhuan Wang , Bo Wang , Yalin Mu , Hui Li
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Abstract

Molecular regulatory mechanism of MAGI2-AS3 in HNSCC is not yet mature.In this study, we analyzed the methylation level of MAGI2-AS3 promoter and its downstream miR-31-5p/AR axis by bioinformatics methods. qRT-PCR was used to detect the mRNA expression level of each gene, and western blot was used to detect the expression level of AR proteins in tissues and cells. CCK-8, colony formation, wound healing, and cellular invasion assays were used to detect the HNSCC cell proliferation, migration, and invasion. Dual luciferase and RIP assays were performed to validate the binding relationship between genes. The effect of MAGI2-AS3 on HNSCC progression was verified in nude mice in vivo.
The low expression of MAGI2-AS3 in HNSCC was caused by hypermethylation of MAGI2-AS3, which could regulate the target of miR-31-5p by sponge adsorption of miR-31-5p, and miR-31-5p could inhibit the expression of AR by directly targeting AR. Thus, MAGI2-AS3 could inhibit the proliferation, migration, and invasion of HNSCC through the miR-31-5p/AR axis. This provided a theoretical basis that MAGI2-AS3 was a potential therapeutic target for HNSCC.
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启动子区MAGI2-AS3高甲基化通过miRNA-31-5p/AR轴促进头颈部鳞状细胞癌的迁移和侵袭。
MAGI2-AS3在HNSCC中的分子调控机制尚不成熟。在本研究中,我们通过生物信息学方法分析了MAGI2-AS3启动子及其下游miR-31-5p/AR轴的甲基化水平。采用qRT-PCR检测各基因mRNA表达水平,western blot检测组织细胞中AR蛋白表达水平。CCK-8、菌落形成、伤口愈合和细胞侵袭试验用于检测HNSCC细胞的增殖、迁移和侵袭。采用双荧光素酶和RIP实验验证基因之间的结合关系。在裸鼠体内验证了MAGI2-AS3对HNSCC进展的影响。mag2 - as3在HNSCC中的低表达是由于mag2 - as3的高甲基化所致,其可通过海绵吸附miR-31-5p调控miR-31-5p的靶点,而miR-31-5p可通过直接靶向AR抑制AR的表达,因此,mag2 - as3可通过miR-31-5p/AR轴抑制HNSCC的增殖、迁移和侵袭。这为MAGI2-AS3是HNSCC的潜在治疗靶点提供了理论依据。
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来源期刊
CiteScore
8.40
自引率
2.00%
发文量
314
审稿时长
54 days
期刊介绍: Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.
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