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...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-03-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/13/4/773 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850155966329257984 |
|---|---|
| author | Zhe Yu Jing Luo Wen An Herui Wei Mengqi Li Lingling He Fan Xiao Hongshan Wei |
| author_facet | Zhe Yu Jing Luo Wen An Herui Wei Mengqi Li Lingling He Fan Xiao Hongshan Wei |
| author_sort | Zhe Yu |
| collection | DOAJ |
| description | <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. |
| format | Article |
| id | doaj-art-8db16e4d285e4f9bbeb0d72e65c0eeea |
| institution | OA Journals |
| issn | 2227-9059 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-8db16e4d285e4f9bbeb0d72e65c0eeea2025-08-20T02:24:43ZengMDPI AGBiomedicines2227-90592025-03-0113477310.3390/biomedicines13040773Migrasome 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 ResistanceZhe Yu0Jing Luo1Wen An2Herui Wei3Mengqi Li4Lingling He5Fan Xiao6Hongshan Wei7Department of Gastroenterology, Peking University Ditan Teaching Hospital, Beijing 100015, ChinaDepartment of Gastroenterology, Peking University Ditan Teaching Hospital, Beijing 100015, ChinaDepartment of Gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, ChinaDepartment of Gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, ChinaDepartment of Gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, ChinaDepartment of Gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, ChinaInstitute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, ChinaDepartment of Gastroenterology, Peking University Ditan Teaching Hospital, Beijing 100015, China<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.https://www.mdpi.com/2227-9059/13/4/773pan-cancer analysis<i>O</i>-GlcNAcylationhepatocellular carcinomaEOGTangiogenesisbiomarker |
| spellingShingle | Zhe Yu Jing Luo Wen An Herui Wei Mengqi Li Lingling He Fan Xiao Hongshan Wei 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 Biomedicines pan-cancer analysis <i>O</i>-GlcNAcylation hepatocellular carcinoma EOGT angiogenesis biomarker |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | pan-cancer analysis <i>O</i>-GlcNAcylation hepatocellular carcinoma EOGT angiogenesis biomarker |
| url | https://www.mdpi.com/2227-9059/13/4/773 |
| work_keys_str_mv | AT zheyu migrasomemarkerepidermalgrowthfactordomainspecificioiglcnactransferasepancancerangiogenesisbiomarkerandthepotentialroleofcirc0058189mir130a3peogtaxisinhepatocellularcarcinomaprogressionandsorafenibresistance AT jingluo migrasomemarkerepidermalgrowthfactordomainspecificioiglcnactransferasepancancerangiogenesisbiomarkerandthepotentialroleofcirc0058189mir130a3peogtaxisinhepatocellularcarcinomaprogressionandsorafenibresistance AT wenan migrasomemarkerepidermalgrowthfactordomainspecificioiglcnactransferasepancancerangiogenesisbiomarkerandthepotentialroleofcirc0058189mir130a3peogtaxisinhepatocellularcarcinomaprogressionandsorafenibresistance AT heruiwei migrasomemarkerepidermalgrowthfactordomainspecificioiglcnactransferasepancancerangiogenesisbiomarkerandthepotentialroleofcirc0058189mir130a3peogtaxisinhepatocellularcarcinomaprogressionandsorafenibresistance AT mengqili migrasomemarkerepidermalgrowthfactordomainspecificioiglcnactransferasepancancerangiogenesisbiomarkerandthepotentialroleofcirc0058189mir130a3peogtaxisinhepatocellularcarcinomaprogressionandsorafenibresistance AT linglinghe migrasomemarkerepidermalgrowthfactordomainspecificioiglcnactransferasepancancerangiogenesisbiomarkerandthepotentialroleofcirc0058189mir130a3peogtaxisinhepatocellularcarcinomaprogressionandsorafenibresistance AT fanxiao migrasomemarkerepidermalgrowthfactordomainspecificioiglcnactransferasepancancerangiogenesisbiomarkerandthepotentialroleofcirc0058189mir130a3peogtaxisinhepatocellularcarcinomaprogressionandsorafenibresistance AT hongshanwei migrasomemarkerepidermalgrowthfactordomainspecificioiglcnactransferasepancancerangiogenesisbiomarkerandthepotentialroleofcirc0058189mir130a3peogtaxisinhepatocellularcarcinomaprogressionandsorafenibresistance |