MiR-548c-3p through suppressing Tyms and Abcg2 increases the sensitivity of colorectal cancer cells to 5-fluorouracil

Background: Colorectal cancer, is one of most prevalent the cancer in the world. 5-Fluorouracil is a standard chemotherapeutic drug while the acquisition of resistance to 5-Fluorouracil is one of the problems during treatment. In this study, we aimed to find the miRNAs that modulate the expression o...

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Main Authors: Elham Khalili, Ali Afgar, Azam Rajabpour, Seyed Hamid Aghaee-Bakhtiari, Khadijeh Jamialahmadi, Ladan Teimoori-Toolabi
Format: Article
Language:English
Published: Elsevier 2023-11-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844023089831
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author Elham Khalili
Ali Afgar
Azam Rajabpour
Seyed Hamid Aghaee-Bakhtiari
Khadijeh Jamialahmadi
Ladan Teimoori-Toolabi
author_facet Elham Khalili
Ali Afgar
Azam Rajabpour
Seyed Hamid Aghaee-Bakhtiari
Khadijeh Jamialahmadi
Ladan Teimoori-Toolabi
author_sort Elham Khalili
collection DOAJ
description Background: Colorectal cancer, is one of most prevalent the cancer in the world. 5-Fluorouracil is a standard chemotherapeutic drug while the acquisition of resistance to 5-Fluorouracil is one of the problems during treatment. In this study, we aimed to find the miRNAs that modulate the expression of Tyms and Abcg2 as resistance-inducing genes in the resistant cell lines to 5-Fluorouracil. Methods: 5-Fluorouracil-resistant HCT116 and SW480 cell lines were generated by consecutive treatment of cells with 5-Fluorouracil. This resistance induction was validated by MTT assays. The expression of the Tyms and Abcg2 gene and miR-548c-3p were studied by quantitative real-time PCR in the cell lines. Results: We hypothesized that miR-548c-3p is targeting Tyms and Abcg2 simultaneously. Increased expression Tyms gene in the two most resistant cell lines derived from HCT116 and all resistant cell lines derived from SW480 except one were seen. Increased expression of Abcg2 was observed in the most resistant HCT116-derived cell line and all resistant cell lines, derived from SW480. In all resistant cell lines, the expression of miR-548c-3p was decreased. Conclusion: It can be concluded downregulation of miR548c-3p is in line with Tyms and Abcg2 overexpression in resistant cell lines to 5-Fluorouracil.
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spelling doaj.art-52ce70e8f52a47a1822533010ad7aa012023-12-02T07:04:12ZengElsevierHeliyon2405-84402023-11-01911e21775MiR-548c-3p through suppressing Tyms and Abcg2 increases the sensitivity of colorectal cancer cells to 5-fluorouracilElham Khalili0Ali Afgar1Azam Rajabpour2Seyed Hamid Aghaee-Bakhtiari3Khadijeh Jamialahmadi4Ladan Teimoori-Toolabi5Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, IranResearch Center for Hydatid Disease in Iran, Kerman University of Medical Sciences, Kerman, IranMolecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, IranDepartment of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranBiotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Corresponding author. Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Iran; Corresponding author. Molecular Medicine Department, Pasteur Institute of Iran, Tehran, IranBackground: Colorectal cancer, is one of most prevalent the cancer in the world. 5-Fluorouracil is a standard chemotherapeutic drug while the acquisition of resistance to 5-Fluorouracil is one of the problems during treatment. In this study, we aimed to find the miRNAs that modulate the expression of Tyms and Abcg2 as resistance-inducing genes in the resistant cell lines to 5-Fluorouracil. Methods: 5-Fluorouracil-resistant HCT116 and SW480 cell lines were generated by consecutive treatment of cells with 5-Fluorouracil. This resistance induction was validated by MTT assays. The expression of the Tyms and Abcg2 gene and miR-548c-3p were studied by quantitative real-time PCR in the cell lines. Results: We hypothesized that miR-548c-3p is targeting Tyms and Abcg2 simultaneously. Increased expression Tyms gene in the two most resistant cell lines derived from HCT116 and all resistant cell lines derived from SW480 except one were seen. Increased expression of Abcg2 was observed in the most resistant HCT116-derived cell line and all resistant cell lines, derived from SW480. In all resistant cell lines, the expression of miR-548c-3p was decreased. Conclusion: It can be concluded downregulation of miR548c-3p is in line with Tyms and Abcg2 overexpression in resistant cell lines to 5-Fluorouracil.http://www.sciencedirect.com/science/article/pii/S2405844023089831Colorectal neoplasmDrug resistance5-FluorouracilTYMS proteinHumanATP binding cassette transporter
spellingShingle Elham Khalili
Ali Afgar
Azam Rajabpour
Seyed Hamid Aghaee-Bakhtiari
Khadijeh Jamialahmadi
Ladan Teimoori-Toolabi
MiR-548c-3p through suppressing Tyms and Abcg2 increases the sensitivity of colorectal cancer cells to 5-fluorouracil
Heliyon
Colorectal neoplasm
Drug resistance
5-Fluorouracil
TYMS protein
Human
ATP binding cassette transporter
title MiR-548c-3p through suppressing Tyms and Abcg2 increases the sensitivity of colorectal cancer cells to 5-fluorouracil
title_full MiR-548c-3p through suppressing Tyms and Abcg2 increases the sensitivity of colorectal cancer cells to 5-fluorouracil
title_fullStr MiR-548c-3p through suppressing Tyms and Abcg2 increases the sensitivity of colorectal cancer cells to 5-fluorouracil
title_full_unstemmed MiR-548c-3p through suppressing Tyms and Abcg2 increases the sensitivity of colorectal cancer cells to 5-fluorouracil
title_short MiR-548c-3p through suppressing Tyms and Abcg2 increases the sensitivity of colorectal cancer cells to 5-fluorouracil
title_sort mir 548c 3p through suppressing tyms and abcg2 increases the sensitivity of colorectal cancer cells to 5 fluorouracil
topic Colorectal neoplasm
Drug resistance
5-Fluorouracil
TYMS protein
Human
ATP binding cassette transporter
url http://www.sciencedirect.com/science/article/pii/S2405844023089831
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