Upregulated m7G methyltransferase METTL1 is a potential biomarker and tumor promoter in skin cutaneous melanoma

Luling XiaPing Yin^*

• Third Xiangya Hospital, Central South University, Changsha, China

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. In vitro 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+ Tcell 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.