AUTHOR=Escalante Paula I. , Quiñones Luis A. , Contreras Héctor R. 

TITLE=Exploring the impact of MiR-92a-3p on FOLFOX chemoresistance biomarker genes in colon cancer cell lines

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1376638

DOI=10.3389/fphar.2024.1376638

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold> 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 (<italic>DPYD</italic>), thymidylate synthase (<italic>TYMS</italic>), methylenetetrahydrofolate reductase (<italic>MTHFR</italic>), and the genes encoding the DNA repair complexes subunits <italic>ERCC1</italic> and <italic>ERCC2</italic>, and <italic>XRCC1</italic>.</p><p><bold>Methods:</bold> To assess this, we transfected SW480 and SW620 colon cancer cell lines with miR-92a-3p mimics and then quantified the expression of <italic>DPYD</italic>, <italic>TYMS</italic>, <italic>MTHFR</italic>, <italic>ERCC1</italic>, <italic>ERCC2</italic>, and <italic>XRCC1</italic>, the expression of EMT markers and transcription factors, and activation of β-catenin.</p><p><bold>Results and discussion:</bold> Our results reveal that miR-92a-3p does not affect the expression of <italic>DPYD</italic>, <italic>TYMS</italic>, <italic>MTHFR</italic>, and <italic>ERCC1.</italic> Furthermore, even though miR-92a-3p affects <italic>ERCC2</italic>, <italic>XRCC1</italic>, E-cadherin, and β-catenin mRNA levels, it has no influence on their protein expression.</p><p><bold>Conclusion:</bold> 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.</p>