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启动子区域高甲基化的MAGI2-AS3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 hypermethylated in promoter region promotes migration and invasion of head and neck squamous cell carcinoma via miRNA-31-5p/AR axis.

作者信息

Yue Kai, Zhang Ting, Wang Huanhuan, Wang Bo, Mu Yalin, Li Hui

机构信息

Department of Oncology, Nanyang Central Hospital, Nanyang 473005, China.

Department of Scientific Research, Nanyang Central Hospital, Nanyang 473005, China.

出版信息

Transl Oncol. 2025 Feb;52:102223. doi: 10.1016/j.tranon.2024.102223. Epub 2024 Dec 7.

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.

摘要

MAGI2-AS3在头颈部鳞状细胞癌中的分子调控机制尚未成熟。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检测各基因的mRNA表达水平,采用蛋白质免疫印迹法检测组织和细胞中AR蛋白的表达水平。采用CCK-8、集落形成、伤口愈合和细胞侵袭实验检测头颈部鳞状细胞癌细胞的增殖、迁移和侵袭能力。进行双荧光素酶和RIP实验以验证基因之间的结合关系。在裸鼠体内验证了MAGI2-AS3对头颈部鳞状细胞癌进展的影响。MAGI2-AS3在头颈部鳞状细胞癌中的低表达是由MAGI2-AS3的高甲基化引起的,其可通过海绵吸附miR-31-5p来调控miR-31-5p的靶标,而miR-31-5p可通过直接靶向AR抑制AR的表达。因此,MAGI2-AS3可通过miR-31-5p/AR轴抑制头颈部鳞状细胞癌的增殖、迁移和侵袭。这为MAGI2-AS3作为头颈部鳞状细胞癌的潜在治疗靶点提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c666/11667182/b51e9057b302/gr1.jpg

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