METTL3 Promotes OSCC Progression by Down-Regulating WEE1 in a m6A-YTHDF2-Dependent Manner.

IF 2.4 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Biotechnology Pub Date : 2025-05-01 Epub Date: 2024-05-14 DOI:10.1007/s12033-024-01165-y

Yongxu Su, Yanjia Hu, Binbin Qu, Rongchang Lei, Ge Guo

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Abstract

Oral squamous cell carcinoma (OSCC) is a common and highly lethal epithelial cancer. This study aimed to confirm the role of METTL3 in promoting OSCC and investigate its specific underlying mechanisms. Expression of the METTL3, YTH domain-containing family 2 (YTHDF2), and WEE1 were examined in normal oral epithelial cells and OSCC cells. Cell functions were examined after overexpressing WEE1 in OSCC cells. MeRIP-qPCR analysis was used to detect WEE1 m6A levels in HOK, SCC25, and CAL27 cells. WEE1 and its m6A levels were evaluated in OSCC cells by knocking down METTL3/YTHDF2, assessing the interaction between METTL3/YTHDF2 and WEE1. The impact of METTL3 and YTHDF2 downregulation on WEE1 mRNA stability was also investigated. The tumor weight and volume in a nude mouse model of OSCC after overexpression of WEE1 and YTHDF2 were measured. Expression of Ki-67 and WEE1 in OSCC tissue was detected using immunohistochemistry. Compared to normal oral epithelial cells, METTL3 and YTHDF2 were upregulated in OSCC cells, while WEE1 was downregulated, and there was a negative correlation between WEE1 and METTL3/YTHDF2 expression. WEE1 overexpression inhibited proliferation, invasion, and migration while promoting apoptosis in OSCC cells. METTL3 and YTHDF2 bound to WEE1 mRNA. METTL3/YTHDF2 knockdown increased WEE1 levels and WEE1 mRNA stability. METTL3 inhibition reduced WEE1 m6A levels. Inhibition of METTL3 weakened the interaction between YTHDF2 and WEE1 mRNA. In vivo, overexpression of WEE1 suppressed OSCC development, which was reversed by overexpression of YTHDF2. METTL3 facilitates the progression of OSCC through m6A-YTHDF2-dependent downregulation of WEE1.

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METTL3 通过依赖 m6A-YTHDF2 下调 WEE1 促进 OSCC 进展

口腔鳞状细胞癌（OSCC）是一种常见的高致死性上皮癌。本研究旨在证实METTL3在促进OSCC中的作用，并研究其具体的内在机制。研究人员检测了METTL3、含YTH结构域的家族2（YTHDF2）和WEE1在正常口腔上皮细胞和OSCC细胞中的表达。在 OSCC 细胞中过表达 WEE1 后，对细胞功能进行了检测。使用 MeRIP-qPCR 分析检测 HOK、SCC25 和 CAL27 细胞中 WEE1 m6A 的水平。通过敲除 METTL3/YTHDF2 评估了 OSCC 细胞中 WEE1 及其 m6A 水平，评估了 METTL3/YTHDF2 与 WEE1 之间的相互作用。此外，还研究了下调 METTL3 和 YTHDF2 对 WEE1 mRNA 稳定性的影响。测定了过表达 WEE1 和 YTHDF2 后 OSCC 裸鼠模型的肿瘤重量和体积。免疫组化法检测了 OSCC 组织中 Ki-67 和 WEE1 的表达。与正常口腔上皮细胞相比，METTL3和YTHDF2在OSCC细胞中上调，而WEE1下调，且WEE1与METTL3/YTHDF2的表达呈负相关。WEE1的过表达抑制了OSCC细胞的增殖、侵袭和迁移，同时促进了细胞凋亡。METTL3 和 YTHDF2 与 WEE1 mRNA 结合。METTL3/YTHDF2的敲除增加了WEE1的水平和WEE1 mRNA的稳定性。抑制 METTL3 可降低 WEE1 m6A 水平。抑制 METTL3 削弱了 YTHDF2 与 WEE1 mRNA 之间的相互作用。在体内，WEE1的过表达抑制了OSCC的发展，而YTHDF2的过表达逆转了这种抑制作用。METTL3通过m6A-YTHDF2依赖性下调WEE1促进了OSCC的进展。

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来源期刊

Molecular Biotechnology 医学-生化与分子生物学

CiteScore

4.10

自引率

3.80%

发文量

165

审稿时长

6 months

期刊介绍： Molecular Biotechnology publishes original research papers on the application of molecular biology to both basic and applied research in the field of biotechnology. Particular areas of interest include the following: stability and expression of cloned gene products, cell transformation, gene cloning systems and the production of recombinant proteins, protein purification and analysis, transgenic species, developmental biology, mutation analysis, the applications of DNA fingerprinting, RNA interference, and PCR technology, microarray technology, proteomics, mass spectrometry, bioinformatics, plant molecular biology, microbial genetics, gene probes and the diagnosis of disease, pharmaceutical and health care products, therapeutic agents, vaccines, gene targeting, gene therapy, stem cell technology and tissue engineering, antisense technology, protein engineering and enzyme technology, monoclonal antibodies, glycobiology and glycomics, and agricultural biotechnology.