N6-Methyladenosine (m6A) modification is one of the commonest chemical modifications in eukaryotic mRNAs, which has essential effects on mRNA translation, splicing, and stability. Currently, there is a rising concern on the regulatory role of m6A in tumorigenesis. As a known component in the m6A methyltransferase complex, METTL3 (methyltransferase-like 3) plays an essential role in m6A methylation. Till now, the functions of METTL3 in oral squamous cell carcinoma (OSCC) and its relative mechanism remain to be explored. In this research, through the GEPIA database, we found that high METTL3 expression has a correlation with poor prognosis of squamous cell carcinoma of head and neck. qRT-PCR displayed that METTL3 was highly expressed in OSCC cells. Functionally, METTL3 knockdown reduced the invasion, migration, and proliferation competence of OSCC cells and attenuated the activation of CD8+ T cells. In contrast, METTL3 overexpression resulted in opposite results. GEPIA, UALCAN, and SRAMP databases, PCR, western blot, and m6A RNA methylation assay confirmed the m6A modification of PRMT5 and PD-L1 mediated by METTL3. In conclusion, our results displayed that METTL3 intensified the metastasis and proliferation of OSCC by modulating the m6A amounts of PRMT5 and PD-L1, suggesting that METTL3 may be a therapeutic target for OSCC patients.

中文翻译：

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METTL3通过调节PRMT5和PD-L1的m6A量促进口腔鳞状细胞癌的进展

N6-甲基腺苷 (m6A) 修饰是真核生物 mRNA 中最常见的化学修饰之一，对 mRNA 的翻译、剪接和稳定性具有重要影响。目前，人们越来越关注m6A在肿瘤发生中的调节作用。作为 m6A 甲基转移酶复合物中的一个已知成分，METTL3（甲基转移酶样 3）在 m6A 甲基化中起重要作用。目前，METTL3在口腔鳞状细胞癌（OSCC）中的作用及其相关机制仍有待探索。本研究通过GEPIA数据库发现METTL3高表达与头颈部鳞状细胞癌预后不良有关。qRT-PCR 显示 METTL3 在 OSCC 细胞中高度表达。在功能上，METTL3 敲低减少了入侵、迁移、和 OSCC 细胞的增殖能力和减弱 CD8+ T 细胞的活化。相反，METTL3 过表达导致相反的结果。GEPIA、UALCAN 和 SRAMP 数据库、PCR、蛋白质印迹和 m6A RNA 甲基化测定证实了 METTL3 介导的 PRMT5 和 PD-L1 的 m6A 修饰。总之，我们的研究结果表明，METTL3 通过调节 PRMT5 和 PD-L1 的 m6A 量来增强 OSCC 的转移和增殖，这表明 METTL3 可能是 OSCC 患者的治疗靶点。