Xia Luling, Yin Ping
Department of Pulmonary and Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, China.
Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Changsha, China.
Front Immunol. 2025 May 15;16:1575219. doi: 10.3389/fimmu.2025.1575219. eCollection 2025.
The m7G methyltransferase METTL1 has been implicated in the occurrence and progression of several cancers. However, its clinical significance in cutaneous melanoma (SKCM) remains poorly understood. To address this gap, we conducted comprehensive data mining using publicly available datasets and two single-cell datasets. Additionally, we employed CCK8 assays, clone formation assays, and cell migration and invasion experiments to validate our findings from the data mining. Our results revealed that METTL1 is significantly upregulated in SKCM and is associated with a stem cell-like phenotype. Patients with high METTL1 expression exhibited worse prognosis. Furthermore, we identified that the high expression of METTL1 in SKCM is driven by copy number amplification and regulated by the transcription factor MYC. cellular studies confirmed that METTL1 knockdown significantly inhibited SKCM cell proliferation, clone formation, migration, and invasion. Notably, we observed a strong negative correlation between METTL1 expression and CD8+ T-cell infiltration in SKCM tissues. Moreover, our analysis revealed a significant negative correlation between METTL1 expression levels and the response to immunotherapy in SKCM patients, suggesting that METTL1 may serve as a potential biomarker for predicting immunotherapy response in SKCM. In summary, this study enhances our understanding of the role of m7G RNA modification in tumor progression and highlights METTL1 as a novel therapeutic target and biomarker for SKCM immunotherapy.
m7G甲基转移酶METTL1与多种癌症的发生和发展有关。然而，其在皮肤黑色素瘤（SKCM）中的临床意义仍知之甚少。为了填补这一空白，我们使用公开可用的数据集和两个单细胞数据集进行了全面的数据挖掘。此外，我们采用CCK8检测、克隆形成检测以及细胞迁移和侵袭实验来验证我们从数据挖掘中获得的结果。我们的结果显示，METTL1在SKCM中显著上调，并与干细胞样表型相关。METTL1高表达的患者预后较差。此外，我们发现SKCM中METTL1的高表达是由拷贝数扩增驱动的，并受转录因子MYC调控。细胞研究证实，敲低METTL1可显著抑制SKCM细胞的增殖、克隆形成、迁移和侵袭。值得注意的是，我们观察到SKCM组织中METTL1表达与CD8 + T细胞浸润之间存在强烈的负相关。此外，我们的分析显示，SKCM患者中METTL1表达水平与免疫治疗反应之间存在显著的负相关，这表明METTL1可能作为预测SKCM免疫治疗反应的潜在生物标志物。总之，本研究增进了我们对m7G RNA修饰在肿瘤进展中作用的理解，并突出了METTL1作为SKCM免疫治疗的新型治疗靶点和生物标志物的地位。
