Transcriptomic characterization revealed that METTL7A inhibits melanoma progression via the p53 signaling pathway and immunomodulatory pathway

Abstract

METTL7A is a protein-coding gene expected to be associated with methylation, and its expression disorder is associated with a range of diseases. However, few research have been carried out to explore the relationship between METTL7A and tumor malignant phenotype as well as the involvement potential mechanism. We conducted our research via a combination of silico analysis and molecular biology techniques to investigate the biological function of METTL7A in the progression of cancer. Gene expression and clinical information were extracted from the TCGA database to explore expression variation and prognostic value of METTL7A. In vitro, CCK8, transwell, wound healing and colony formation assays were conducted to explore the biological functions of METT7A in cancer cell. GSEA was performed to explore the signaling pathway involved in METTL7A and validated via western blotting. In conclusion, METTL7A was downregulated in most cancer tissues and its low expression was associated with shorter overall survival. In melanoma, METTL7A downregulation was associated with poorer clinical staging, lower levels of TIL infiltration, higher IC50 levels of chemotherapeutic agents, and poorer immunotherapy outcomes. QPCR results confirm that METTL7A is down-regulated in melanoma cells. Cell function assays showed that METTL7A knockdown promoted proliferation, invasion, migration and clone formation of melanoma cells. Mechanistic studies showed that METTL7A inhibits tumorigenicity through the p53 signaling pathway. Meanwhile, METTL7A is also a potential immune regulatory factor.

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“…In contrast, METTL7A plays a role in the translational regulation of cell biological processes. Some studies have reported that METTL7A can activate immune-related pathways and the P53 signaling pathway to inhibit melanoma progression . Furthermore, DNA methylation by METTL7A promotes osteogenic and odontogenic differentiation by upregulating gene expression, which in turn promotes differentiation and survival .…”

“…Some studies have reported that METTL7A can activate immune-related pathways and the P53 signaling pathway to inhibit melanoma progression. 56 Furthermore, DNA methylation by METTL7A promotes osteogenic and odontogenic differentiation by upregulating gene expression, which in turn promotes differentiation and survival. 30 The above reports indicate that METTL7A targets the transcriptional regulation of genes by alteration of DNA methylation.…”