METTL3 modulates m6A modification of CDC25B and promotes head and neck squamous cell carcinoma malignant progression.

METTL3 modulates m6A modification of CDC25B and promotes head and neck squamous cell carcinoma malignant progression.
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METTL3调节CDC25B的m6A修饰促进头颈鳞状细胞癌恶性进展

DOI:
10.1186/s40164-022-00256-3
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发表时间:
2022-03-14
影响因子:
10.9
通讯作者:
Gao X
Gao X
中科院分区:
医学2区
文献类型:
--
作者:
Guo YQ;Wang Q;Wang JG;Gu YJ;Song PP;Wang SY;Qian XY;Gao X

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N6-甲基腺苷(m6 A)RNA甲基化及其甲基转移酶L3被广泛报道通过调节RNA代谢和功能参与不同的癌症。本研究旨在探讨m6 A修饰和胃L3在头颈部鳞状细胞癌中的生物学功能及临床意义。采用组织微阵列和免疫组化染色分析评估了人HNSCC队列中胃L3表达的预后价值。在体外和体内研究了胃L3在HNSCC肿瘤生长、转移和血管生成中的生物学作用和机制。HNSCC组织中M6 A和胃L3的表达较癌旁组织明显增高。同时,胃L3是影响HNSCC患者预后的独立危险因素。此外,过表达胃L3促进HNSCC细胞增殖、迁移、侵袭和血管生成,而敲低胃L3在体内和体外具有相反的作用。在机制上,胃L3增强了CDC 25 B mRNA的m6 A修饰,从而维持其稳定性并上调其表达,从而激活细胞周期的G2/M期,导致HNSCC恶性进展。胃L3可能是HNSCC潜在的预后生物标志物和治疗靶点。在线版本包含补充材料,可通过10.1186/s40164-022-00256-3获得。
N6-methyladenosine (m6A) RNA methylation and its methyltransferase METTL3 have been widely reported to be involved in different cancers by regulating RNA metabolism and function. Here, we aimed to explore the biological function and clinical significance of m6A modification and METTL3 in head and neck squamous cell carcinoma (HNSCC). The prognostic value of METTL3 expression was evaluated using tissue microarray and immunohistochemical staining analyses in a human HNSCC cohort. The biological role and mechanism of METTL3 in HNSCC tumour growth, metastasis and angiogenesis were determined in vitro and in vivo. M6A levels and METTL3 expressions in HNSCC tissues were significantly increased compared with paired adjacent tissues. Meanwhile, METTL3 was an independent risk factor for the prognosis of HNSCC patients. Moreover, METTL3 overexpression promoted HNSCC cell proliferation, migration, invasion, and angiogenesis, while knockdown of METTL3 had an opposite effect in vivo and in vitro. Mechanistically, METTL3 enhanced the m6A modification of CDC25B mRNA, which maintained its stability and upregulated its expression, thereby activating G2/M phase of cell cycle and leading to HNSCC malignant progression. METTL3 may be a potential prognostic biomarker and therapeutic target for HNSCC. The online version contains supplementary material available at 10.1186/s40164-022-00256-3.
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