Exploring the impact of MiR-92a-3p on FOLFOX chemoresistance biomarker genes in colon cancer cell lines
Introduction: One of the primary obstacles faced by individuals with advanced colorectal cancer (CRC) is the potential development of acquired chemoresistance as the disease advances. Studies have indicated a direct association between elevated levels of miR-92a-3p and the progression, metastasis, a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1376638/full |
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| author | Paula I. Escalante Paula I. Escalante Luis A. Quiñones Luis A. Quiñones Luis A. Quiñones Héctor R. Contreras Héctor R. Contreras |
| author_facet | Paula I. Escalante Paula I. Escalante Luis A. Quiñones Luis A. Quiñones Luis A. Quiñones Héctor R. Contreras Héctor R. Contreras |
| author_sort | Paula I. Escalante |
| collection | DOAJ |
| description | Introduction: One of the primary obstacles faced by individuals with advanced colorectal cancer (CRC) is the potential development of acquired chemoresistance as the disease advances. Studies have indicated a direct association between elevated levels of miR-92a-3p and the progression, metastasis, and chemoresistance observed in CRC. We proposed that miR-92a-3p impairs FOLFOX (fluorouracil/oxaliplatin) chemotherapy response by upregulating the expression of chemoresistance biomarker genes through the activation of β-catenin and epithelial-mesenchymal transition (EMT). These FOLFOX biomarker genes include the pyrimidine biosynthesis pathway genes dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), and the genes encoding the DNA repair complexes subunits ERCC1 and ERCC2, and XRCC1.Methods: To assess this, we transfected SW480 and SW620 colon cancer cell lines with miR-92a-3p mimics and then quantified the expression of DPYD, TYMS, MTHFR, ERCC1, ERCC2, and XRCC1, the expression of EMT markers and transcription factors, and activation of β-catenin.Results and discussion: Our results reveal that miR-92a-3p does not affect the expression of DPYD, TYMS, MTHFR, and ERCC1. Furthermore, even though miR-92a-3p affects ERCC2, XRCC1, E-cadherin, and β-catenin mRNA levels, it has no influence on their protein expression.Conclusion: We found that miR-92a-3p does not upregulate the expression of proteins of DNA-repair pathways and other genes involved in FOLFOX chemotherapy resistance. |
| first_indexed | 2024-04-24T11:37:31Z |
| format | Article |
| id | doaj.art-a31bbc1af431457ba87c309b6ee6d65b |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-24T11:37:31Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-a31bbc1af431457ba87c309b6ee6d65b2024-04-10T04:46:08ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-04-011510.3389/fphar.2024.13766381376638Exploring the impact of MiR-92a-3p on FOLFOX chemoresistance biomarker genes in colon cancer cell linesPaula I. Escalante0Paula I. Escalante1Luis A. Quiñones2Luis A. Quiñones3Luis A. Quiñones4Héctor R. Contreras5Héctor R. Contreras6Laboratory of Chemical Carcinogenesis and Pharmacogenetics (CQF), Department of Basic and Clinical Oncology (DOBC), Faculty of Medicine, University of Chile, Santiago, ChileLaboratory of Cellular and Molecular Oncology (LOCYM), Department of Basic and Clinical Oncology (DOBC), Faculty of Medicine, University of Chile, Santiago, ChileLaboratory of Chemical Carcinogenesis and Pharmacogenetics (CQF), Department of Basic and Clinical Oncology (DOBC), Faculty of Medicine, University of Chile, Santiago, ChileLatin American Network for the Implementation and Validation of Pharmacogenomic Clinical Guidelines (RELIVAF), Santiago, ChileDepartment of Pharmaceutical Sciences and Technology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, ChileLaboratory of Cellular and Molecular Oncology (LOCYM), Department of Basic and Clinical Oncology (DOBC), Faculty of Medicine, University of Chile, Santiago, ChileCenter for Cancer Prevention and Control (CECAN), Santiago, ChileIntroduction: One of the primary obstacles faced by individuals with advanced colorectal cancer (CRC) is the potential development of acquired chemoresistance as the disease advances. Studies have indicated a direct association between elevated levels of miR-92a-3p and the progression, metastasis, and chemoresistance observed in CRC. We proposed that miR-92a-3p impairs FOLFOX (fluorouracil/oxaliplatin) chemotherapy response by upregulating the expression of chemoresistance biomarker genes through the activation of β-catenin and epithelial-mesenchymal transition (EMT). These FOLFOX biomarker genes include the pyrimidine biosynthesis pathway genes dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), and the genes encoding the DNA repair complexes subunits ERCC1 and ERCC2, and XRCC1.Methods: To assess this, we transfected SW480 and SW620 colon cancer cell lines with miR-92a-3p mimics and then quantified the expression of DPYD, TYMS, MTHFR, ERCC1, ERCC2, and XRCC1, the expression of EMT markers and transcription factors, and activation of β-catenin.Results and discussion: Our results reveal that miR-92a-3p does not affect the expression of DPYD, TYMS, MTHFR, and ERCC1. Furthermore, even though miR-92a-3p affects ERCC2, XRCC1, E-cadherin, and β-catenin mRNA levels, it has no influence on their protein expression.Conclusion: We found that miR-92a-3p does not upregulate the expression of proteins of DNA-repair pathways and other genes involved in FOLFOX chemotherapy resistance.https://www.frontiersin.org/articles/10.3389/fphar.2024.1376638/fullmiR-92a-3pDPYDTYMSMTHFRERCC2XRCC1 |
| spellingShingle | Paula I. Escalante Paula I. Escalante Luis A. Quiñones Luis A. Quiñones Luis A. Quiñones Héctor R. Contreras Héctor R. Contreras Exploring the impact of MiR-92a-3p on FOLFOX chemoresistance biomarker genes in colon cancer cell lines Frontiers in Pharmacology miR-92a-3p DPYD TYMS MTHFR ERCC2 XRCC1 |
| title | Exploring the impact of MiR-92a-3p on FOLFOX chemoresistance biomarker genes in colon cancer cell lines |
| title_full | Exploring the impact of MiR-92a-3p on FOLFOX chemoresistance biomarker genes in colon cancer cell lines |
| title_fullStr | Exploring the impact of MiR-92a-3p on FOLFOX chemoresistance biomarker genes in colon cancer cell lines |
| title_full_unstemmed | Exploring the impact of MiR-92a-3p on FOLFOX chemoresistance biomarker genes in colon cancer cell lines |
| title_short | Exploring the impact of MiR-92a-3p on FOLFOX chemoresistance biomarker genes in colon cancer cell lines |
| title_sort | exploring the impact of mir 92a 3p on folfox chemoresistance biomarker genes in colon cancer cell lines |
| topic | miR-92a-3p DPYD TYMS MTHFR ERCC2 XRCC1 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1376638/full |
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