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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| Vydáno v: | Frontiers in pharmacology Ročník 15; s. 1376638 |
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| Hlavní autoři: | , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
Switzerland
Frontiers Media S.A
10.04.2024
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| Témata: | |
| ISSN: | 1663-9812, 1663-9812 |
| On-line přístup: | Získat plný text |
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| Shrnutí: | 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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| Bibliografie: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 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 |