ACSL3 is an unfavorable prognostic marker in cholangiocarcinoma patients and confers ferroptosis resistance in cholangiocarcinoma cells
Abstract Cholangiocarcinoma (CCA) is a bile duct malignancy. Our previous comprehensive analysis showed that ferroptosis-related genes can stratify CCA patients into low-risk and high-risk groups based on survival time. Here, we explored the role of ferroptosis in CCA by analyzing mRNA expression in...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-12-01
|
| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-024-00783-8 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850244695458840576 |
|---|---|
| author | Apiwit Sae-Fung Nawaporn Vinayavekhin Bengt Fadeel Siriporn Jitkaew |
| author_facet | Apiwit Sae-Fung Nawaporn Vinayavekhin Bengt Fadeel Siriporn Jitkaew |
| author_sort | Apiwit Sae-Fung |
| collection | DOAJ |
| description | Abstract Cholangiocarcinoma (CCA) is a bile duct malignancy. Our previous comprehensive analysis showed that ferroptosis-related genes can stratify CCA patients into low-risk and high-risk groups based on survival time. Here, we explored the role of ferroptosis in CCA by analyzing mRNA expression in CCA patients from public databases. We identified acyl-CoA synthetase long chain family member 3 (ACSL3) as a potential ferroptosis suppressor in high-risk CCA patients. Using a panel of CCA cell lines, we confirmed ACSL3 upregulation in CCA cell lines associated with high-risk CCA, correlating this with resistance to the ferroptosis inducer RSL3. Lipidomic analysis revealed increased monounsaturated fatty acid (MUFA)-containing phospholipids in resistant cell lines. ACSL3 silencing sensitized these cells to RSL3. Resistance to ferroptosis was also dependent on exogenous MUFAs and was enhanced by lipid droplet biogenesis inhibition. These findings highlight ACSL3 as a promising target for therapeutic strategies aimed at overcoming ferroptosis resistance in CCA. |
| format | Article |
| id | doaj-art-cc181eb5ddd841d5ae849fb6ef0e9dde |
| institution | OA Journals |
| issn | 2397-768X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-cc181eb5ddd841d5ae849fb6ef0e9dde2025-08-20T01:59:39ZengNature Portfolionpj Precision Oncology2397-768X2024-12-018111410.1038/s41698-024-00783-8ACSL3 is an unfavorable prognostic marker in cholangiocarcinoma patients and confers ferroptosis resistance in cholangiocarcinoma cellsApiwit Sae-Fung0Nawaporn Vinayavekhin1Bengt Fadeel2Siriporn Jitkaew3Graduate Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn UniversityCenter of Excellence in Natural Products Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn UniversityDivision of Molecular Toxicology, Institute of Environmental Medicine, Karolinska InstitutetCenter of Excellence for Cancer and Inflammation, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn UniversityAbstract Cholangiocarcinoma (CCA) is a bile duct malignancy. Our previous comprehensive analysis showed that ferroptosis-related genes can stratify CCA patients into low-risk and high-risk groups based on survival time. Here, we explored the role of ferroptosis in CCA by analyzing mRNA expression in CCA patients from public databases. We identified acyl-CoA synthetase long chain family member 3 (ACSL3) as a potential ferroptosis suppressor in high-risk CCA patients. Using a panel of CCA cell lines, we confirmed ACSL3 upregulation in CCA cell lines associated with high-risk CCA, correlating this with resistance to the ferroptosis inducer RSL3. Lipidomic analysis revealed increased monounsaturated fatty acid (MUFA)-containing phospholipids in resistant cell lines. ACSL3 silencing sensitized these cells to RSL3. Resistance to ferroptosis was also dependent on exogenous MUFAs and was enhanced by lipid droplet biogenesis inhibition. These findings highlight ACSL3 as a promising target for therapeutic strategies aimed at overcoming ferroptosis resistance in CCA.https://doi.org/10.1038/s41698-024-00783-8 |
| spellingShingle | Apiwit Sae-Fung Nawaporn Vinayavekhin Bengt Fadeel Siriporn Jitkaew ACSL3 is an unfavorable prognostic marker in cholangiocarcinoma patients and confers ferroptosis resistance in cholangiocarcinoma cells npj Precision Oncology |
| title | ACSL3 is an unfavorable prognostic marker in cholangiocarcinoma patients and confers ferroptosis resistance in cholangiocarcinoma cells |
| title_full | ACSL3 is an unfavorable prognostic marker in cholangiocarcinoma patients and confers ferroptosis resistance in cholangiocarcinoma cells |
| title_fullStr | ACSL3 is an unfavorable prognostic marker in cholangiocarcinoma patients and confers ferroptosis resistance in cholangiocarcinoma cells |
| title_full_unstemmed | ACSL3 is an unfavorable prognostic marker in cholangiocarcinoma patients and confers ferroptosis resistance in cholangiocarcinoma cells |
| title_short | ACSL3 is an unfavorable prognostic marker in cholangiocarcinoma patients and confers ferroptosis resistance in cholangiocarcinoma cells |
| title_sort | acsl3 is an unfavorable prognostic marker in cholangiocarcinoma patients and confers ferroptosis resistance in cholangiocarcinoma cells |
| url | https://doi.org/10.1038/s41698-024-00783-8 |
| work_keys_str_mv | AT apiwitsaefung acsl3isanunfavorableprognosticmarkerincholangiocarcinomapatientsandconfersferroptosisresistanceincholangiocarcinomacells AT nawapornvinayavekhin acsl3isanunfavorableprognosticmarkerincholangiocarcinomapatientsandconfersferroptosisresistanceincholangiocarcinomacells AT bengtfadeel acsl3isanunfavorableprognosticmarkerincholangiocarcinomapatientsandconfersferroptosisresistanceincholangiocarcinomacells AT siripornjitkaew acsl3isanunfavorableprognosticmarkerincholangiocarcinomapatientsandconfersferroptosisresistanceincholangiocarcinomacells |