Migrasome Marker Epidermal Growth Factor Domain-Specific <i>O</i>-GlcNAc Transferase: Pan-Cancer Angiogenesis Biomarker and the Potential Role of circ_0058189/miR-130a-3p/EOGT Axis in Hepatocellular Carcinoma Progression and Sorafenib Resistance
<b>Background</b>: The EGF domain-specific O-GlcNAc transferase (EOGT), a migrasome marker, plays emerging roles in cancer biology through O-GlcNAcylation modifications, yet its pan-cancer functions and therapeutic implications remain underexplored. This study aimed to systematically cha...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-03-01
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| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/13/4/773 |
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| Summary: | <b>Background</b>: The EGF domain-specific O-GlcNAc transferase (EOGT), a migrasome marker, plays emerging roles in cancer biology through O-GlcNAcylation modifications, yet its pan-cancer functions and therapeutic implications remain underexplored. This study aimed to systematically characterize EOGT’s oncogenic mechanisms across malignancies, with particular focus on hepatocellular carcinoma (HCC) progression and sorafenib resistance. <b>Methods</b>: Multi-omics analysis integrated TCGA/GTEx data from 33 cancer types with spatial/single-cell transcriptomics and 10 HCC cohorts. Functional validation employed Huh7 cell models with <i>EOGT</i> modulation, RNA sequencing, and ceRNA network construction. Drug sensitivity analysis leveraged GDSC/CTRP/PRISM databases, while immune microenvironment assessment utilized ESTIMATE/TIMER algorithms. <b>Results</b>: <i>EOGT</i> showed cancer-specific dysregulation, marked by significant upregulation in HCC correlating with advanced stages and poor survival. Pan-cancer analysis revealed <i>EOGT</i>’s association with genomic instability, tumor stemness, and angiogenesis. Experimental validation demonstrated EOGT’s promotion of HCC proliferation and migration. A novel exosomal circ_0058189/miR-130a-3p/EOGT axis was identified, showing that circ_0058189 was upregulated in HCC tissues, plasma samples and exosomes of sorafenib-resistant cells. <b>Conclusion</b>: This study establishes EOGT as a pan-cancer angiogenesis biomarker, while elucidating its role in therapeutic resistance via exosomal circRNA-mediated regulation, providing mechanistic insights for targeted intervention strategies. |
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| ISSN: | 2227-9059 |