State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
Mol Biomed. 2024 Jul 16;5(1):27. doi: 10.1186/s43556-024-00189-9.
miRNA has emerged as a crucial regulator in various of pathological and physiological processes, yet its precise mechanism of action the detailed mechanism of their action in Head and neck squamous cell carcinoma (HNSCC) remains incompletely understood. This study sheds light on the role of mi-151-5p, revealing its significantly elevated expression in tumor cells, which notably enhances the invasion and migration of HNSCC cells. This effect is achieved through directly targeting LY6/PLAUR Domain Containing 3 (LYPD3) by miR-151-5p, involving complementary binding to the 3'-untranslated regions (3'-UTR) in the mRNA of LYPD3. Consequently, this interaction accelerates the metastasis of HNSCC. Notably, clinical observations indicate a correlation between high expression of miR-151-5p and low levels of LYPD3 in clinical settings are correlated with poor prognosis of HNSCC patients. Furthermore, our investigation demonstrates that glycosylation of LYPD3 modulates its subcellular localization and reinforces its role in suppressing HNSCC metastasis. Additionally, we uncover a potential regulatory mechanism involving the facilitation of miR-151-5p maturation and accumulation through N6-methyladenosine (m6A) modification. This process is orchestrated by methyltransferase-like 3 (METTL3) and mediated by a newly identified reader, heterogeneous nuclear ribonucleoprotein U (hnRNP U). These findings collectively underscore the significance of the METTL3/miR-151-5p/LYPD3 axis serves as a prominent driver in the malignant progression of HNSCC.
miRNA 已成为各种病理和生理过程中的关键调节因子，但其在头颈部鳞状细胞癌 (HNSCC) 中的确切作用机制仍不完全清楚。本研究揭示了 miR-151-5p 的作用，发现其在肿瘤细胞中显著上调，显著增强了 HNSCC 细胞的侵袭和迁移能力。这种效应是通过 miR-151-5p 直接靶向 LY6/PLAUR 结构域包含 3 号（LYPD3）实现的，涉及与 LYPD3 mRNA 的 3'-非翻译区（3'-UTR）的互补结合。因此，这种相互作用加速了 HNSCC 的转移。值得注意的是，临床观察表明，miR-151-5p 高表达与 LYPD3 低表达与 HNSCC 患者预后不良相关。此外，我们的研究表明，LYPD3 的糖基化调节其亚细胞定位，并增强其抑制 HNSCC 转移的作用。此外，我们发现了一个潜在的调节机制，涉及通过 N6-甲基腺苷（m6A）修饰促进 miR-151-5p 的成熟和积累。这个过程由甲基转移酶样 3（METTL3）协调，并由新发现的阅读器异质核核糖核蛋白 U（hnRNP U）介导。这些发现共同强调了 METTL3/miR-151-5p/LYPD3 轴作为 HNSCC 恶性进展的主要驱动因素的重要性。
