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

Paula I Escalante ^1,2, Luis A Quiñones ^1,3,4, Héctor R Contreras ^2,5

⁰Laboratory of Chemical Carcinogenesis and Pharmacogenetics (CQF), Department of Basic and Clinical Oncology (DOBC), Faculty of Medicine, University of Chile, Santiago, Chile.

Frontiers in Pharmacology +

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April 25, 2024

View abstract on PubMed

Summary

MicroRNA-92a-3p does not increase chemoresistance in colorectal cancer. This study found no evidence that miR-92a-3p upregulates key proteins involved in FOLFOX resistance, impacting treatment strategies for advanced colorectal cancer.

Area Of Science

Oncology
Molecular Biology
Genetics

Background

Acquired chemoresistance is a major challenge in advanced colorectal cancer (CRC).
Elevated miR-92a-3p levels are linked to CRC progression, metastasis, and chemoresistance.
miR-92a-3p is hypothesized to impair FOLFOX chemotherapy response via β-catenin and EMT activation.

Purpose Of The Study

To investigate the role of miR-92a-3p in FOLFOX chemotherapy resistance in CRC.
To determine if miR-92a-3p upregulates chemoresistance biomarker genes, including DNA repair and pyrimidine biosynthesis pathway genes.
To assess the impact of miR-92a-3p on β-catenin and epithelial-mesenchymal transition (EMT) markers.

Main Methods

Transfection of SW480 and SW620 colon cancer cell lines with miR-92a-3p mimics.
Quantification of gene expression for DPYD, TYMS, MTHFR, ERCC1, ERCC2, and XRCC1.
Assessment of EMT markers, transcription factors, and β-catenin activation.

Main Results

miR-92a-3p did not affect the expression of DPYD, TYMS, MTHFR, and ERCC1.
While miR-92a-3p influenced mRNA levels of ERCC2, XRCC1, E-cadherin, and β-catenin, it did not alter their protein expression.
The study did not find evidence of miR-92a-3p upregulating key proteins involved in FOLFOX resistance.

Conclusions

miR-92a-3p does not appear to upregulate proteins in DNA-repair pathways or other genes contributing to FOLFOX chemotherapy resistance in CRC.
These findings suggest miR-92a-3p may not be a direct driver of FOLFOX resistance through the proposed mechanisms.
Further research is needed to fully elucidate the role of microRNAs in CRC chemoresistance.

Keywords:

DPYD ERCC2 MTHFR TYMS XRCC1 chemoresistance miR-92a-3p pharmacoepigenetics

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