Investigating the role of miRNA-98 and miRNA-214 in chemoresistance of HepG2/Dox cells: studying their effects on predicted ABC transporters targets
Multidrug resistance (MDR) remains a burden in cancer chemotherapy. Several members of ATP-binding cassette (ABC transporters) are responsible for the efflux of anticancer drugs outside cells decreasing the drug’s effective intracellular concentration. Therefore, extensive efforts have been conducted by researcher to circumvent the activity of these transporters to enhance the success of chemotherapy. In the present study, we questioned the role played by two microRNAs, namely miR-98 and miR-214 in controlling their bioinformatics’ predicted ABC efflux transporter targets ABCC5 and ABCC10, in addition to ABCB1 and ABCC1 in doxorubicin-resistant HCC cells (HepG2/Dox). miRNA mimics and inhibitors transfection were utilized to explore the role of both candidate molecules in MDR in HepG2/Dox cells. QRT-PCR and western blotting were used for quantitative gene and protein analyses. The study revealed that miR-214 mimics significantly upregulated ABCC1 and ABCC5. While, miR-98 and miR-214 inhibitors significantly down regulated ABCC5 and ABCC10, respectively. These results introduced a possible negative role played by both miR-98 and miR-214 on drug sensitization. Moreover, these findings clarified that the predicted targets for miR-98 and miR-214 were not confirmed experimentally.
KeywordsMDR miR-98 miR-214 ABCC5 ABCC10
This work was supported by grants from Science and technology development fund (STDF), Egypt, Basic and applied research grant (Project ID: 4361). We thank Salma M. Abdelnasser and Gamal Eldein F. Abd-Ellatef for technical help.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
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