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, 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.