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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Published in:Frontiers in pharmacology Vol. 15; p. 1376638
Main Authors: Escalante, Paula I., Quiñones, Luis A., Contreras, Héctor R.
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 10.04.2024
Subjects:
DPYD
ERCC2
miR-92a-3p
MTHFR
Pharmacology
TYMS
XRCC1
pharmacoepigenetics
chemoresistance
DPYD
ERCC2
miR-92a-3p
MTHFR
XRCC1
TYMS
ISSN:1663-9812, 1663-9812
Online Access:Get full text
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Summary: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.
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Reviewed by: Lalit Kaurani, Helmholtz Association of German Research Centers (HZ), Germany
Edited by: Urs Heilbronner, LMU Munich University Hospital, Germany
Zhipeng Liu, Purdue University, United States
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2024.1376638