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Background <p>Skin cutaneous melanoma (SKCM) is one of the highly malignant tumor. This study aimed to investigate the expression levels of MTHFD1L in cutaneous melanoma and to uncover its potential biological significance.</p> Methods <p>This investigation employed the TCGA-SKCM dataset along with combined GSE15605 and GSE19234 datasets to analyze MTHFD1L expression patterns. Comprehensive bioinformatics analyses were conducted, including GO and KEGG pathway enrichment analyses, protein-protein interaction network construction, and evaluation of the relationship between MTHFD1L expression and immune infiltration. Prognostic significance was assessed using the GEPIA2 database. Experimental validation involved: (1) RT-qPCR, Western blot, and IHC staining to compare MTHFD1L expression between SKCM and normal tissues; (2) establishment of MTHFD1L knockdown models in A375 and 2058 cell lines for functional characterization.</p> Results <p>The MTHFD1L level was increasing in SKCM tissues from GSE15605/GSE19234 and TCGA-SKCM, and high MTHFD1L expression correlated with poor overall survival. The RT-qPCR, Western blot and IHC confirmed the accuracy of bioinformatics. Knockdown of MTHFD1L significantly inhibited proliferation, migration, invasion, and clonogenic ability in A375 and A2058 melanoma cells, potentially through regulation of the TGF-β/SMAD signaling pathway.</p> Conclusion <p>MTHFD1L is a potential biomarker in cutaneous melanoma, and could potentially serve as a therapeutic target for SKCM.</p>

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MTHFD1L is a novel prognostic marker and therapeutic target in cutaneous melanoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月10日

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  • Xinlian Xie,
  • Guangfu Shi,
  • Kebin Ning,
  • Zhenjie Wu

摘要

Background

Skin cutaneous melanoma (SKCM) is one of the highly malignant tumor. This study aimed to investigate the expression levels of MTHFD1L in cutaneous melanoma and to uncover its potential biological significance.

Methods

This investigation employed the TCGA-SKCM dataset along with combined GSE15605 and GSE19234 datasets to analyze MTHFD1L expression patterns. Comprehensive bioinformatics analyses were conducted, including GO and KEGG pathway enrichment analyses, protein-protein interaction network construction, and evaluation of the relationship between MTHFD1L expression and immune infiltration. Prognostic significance was assessed using the GEPIA2 database. Experimental validation involved: (1) RT-qPCR, Western blot, and IHC staining to compare MTHFD1L expression between SKCM and normal tissues; (2) establishment of MTHFD1L knockdown models in A375 and 2058 cell lines for functional characterization.

Results

The MTHFD1L level was increasing in SKCM tissues from GSE15605/GSE19234 and TCGA-SKCM, and high MTHFD1L expression correlated with poor overall survival. The RT-qPCR, Western blot and IHC confirmed the accuracy of bioinformatics. Knockdown of MTHFD1L significantly inhibited proliferation, migration, invasion, and clonogenic ability in A375 and A2058 melanoma cells, potentially through regulation of the TGF-β/SMAD signaling pathway.

Conclusion

MTHFD1L is a potential biomarker in cutaneous melanoma, and could potentially serve as a therapeutic target for SKCM.