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VIRMA 通过调节 mRNA 和 m6A 水平促进头颈部鳞状细胞癌的进展。

VIRMA promotes the progression of head and neck squamous cell carcinoma by regulating mRNA and m6A levels.

机构信息

Department of Oral and Maxillofacial Surgery, School of Stomatology and Stomatological Hospital, Hebei Medical University, Shijiazhuang, China.

The Key Laboratory of Oral Medicine in Hebei Province, School of Stomatology and Stomatological Hospital, Hebei Medical University, Shijiazhuang, China.

出版信息

Biomol Biomed. 2024 Sep 6;24(5):1244-1257. doi: 10.17305/bb.2024.10358.

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a globally prevalent and lethal cancer form which precise mechanisms remain incompletely understood. Increasing evidence suggests that N6-methyladenosine (m6A) plays a crucial role in cancer progression. This study aimed to explore the biological function of m6A modification and vir-like m6A methyltransferase associated (VIRMA) in HNSCC. We conducted an analysis of VIRMA expression in HNSCC cells using The Cancer Genome Atlas (TCGA) database and employed reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting to assess its expression levels in HNSCC cell lines. Additionally, m6A levels in HNSCC cells were quantified, and the correlation between VIRMA expression levels and the clinical and pathological features of other genes was analyzed. Upon knocking down VIRMA levels, we assessed HNSCC cell proliferation, migration, and invasion and validated downstream genes using RT-qPCR and western blot. Our findings suggested that VIRMA, as an m6A-related regulator, may significantly influence HNSCC progression by regulating ubiquitin protein ligase E3 component N-recognin 5 (UBR5) through m6A modification. Therefore, VIRMA may serve as a prognostic biomarker.

摘要

头颈部鳞状细胞癌(HNSCC)是一种全球普遍存在且致命的癌症形式,其确切机制仍不完全清楚。越来越多的证据表明,N6-甲基腺苷(m6A)在癌症进展中起着关键作用。本研究旨在探讨 m6A 修饰和病毒样 m6A 甲基转移酶相关(VIRMA)在 HNSCC 中的生物学功能。我们使用癌症基因组图谱(TCGA)数据库分析了 HNSCC 细胞中的 VIRMA 表达,并采用逆转录定量聚合酶链反应(RT-qPCR)和蛋白质印迹法检测 HNSCC 细胞系中的表达水平。此外,我们还定量了 HNSCC 细胞中的 m6A 水平,并分析了 VIRMA 表达水平与其他基因的临床和病理特征之间的相关性。在下调 VIRMA 水平后,我们评估了 HNSCC 细胞的增殖、迁移和侵袭,并使用 RT-qPCR 和蛋白质印迹法验证了下游基因。我们的研究结果表明,VIRMA 作为一种与 m6A 相关的调节剂,可能通过 m6A 修饰调节泛素蛋白连接酶 E3 成分 N-识别蛋白 5(UBR5),从而显著影响 HNSCC 的进展。因此,VIRMA 可能成为一种预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e65/11379021/4f606a65a2ca/bb-2024-10358f1.jpg

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