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Open AccessArticle

miR-23b Modulates the Epithelial–Mesenchymal Transition of Colorectal Cancer Cells

1
Institute of Biotechnology, Life Sciences Center, Vilnius University, LT-10257 Vilnius, Lithuania
2
Institute of Biochemistry, Life Sciences Center, Vilnius University, LT-10257 Vilnius, Lithuania
3
Thermo Fisher Scientific Baltics, LT-02241 Vilnius, Lithuania
4
National Center of Pathology, Affiliate of Vilnius University Hospital Santaros Klinikos, LT-08406 Vilnius, Lithuania
5
Faculty of Medicine, Vilnius University, Vilnius, LT-03101, Lithuania
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this manuscript.
J. Clin. Med. 2019, 8(12), 2115; https://doi.org/10.3390/jcm8122115
Received: 17 October 2019 / Revised: 27 November 2019 / Accepted: 29 November 2019 / Published: 2 December 2019
(This article belongs to the Special Issue Molecular Mechanisms of Cancer Chemoprevention)
Although treatment of colorectal cancer with 5-florouracil and oxaliplatin is widely used, it is frequently followed by a relapse. Therefore, there is an urgent need for profound understanding of chemotherapy resistance mechanisms as well as the profiling of predictive markers for individualized treatment. In this study, we identified the changes in 14 miRNAs in 5-fluouracil and 40 miRNAs in oxaliplatin-resistant cell lines by miRNA sequencing. The decrease in miR-224-5p expression in the 5-fluorouracil-resistant cells correlated with drug insensitivity due to its overexpression-induced drug-dependent apoptosis. On the other hand, the miR-23b/27b/24-1 cluster was overexpressed in oxaliplatin-resistant cells. The knockout of miR-23b led to the partial restoration of oxaliplatin susceptibility, showing the essential role of miR-23b in the development of drug resistance by this cluster. Proteomic analysis identified target genes of miR-23b and showed that endothelial–mesenchymal transition (EMT) was implicated in oxaliplatin insensibility. Data revealed that EMT markers, such as vimentin and SNAI2, were expressed moderately higher in the oxaliplatin-resistant cells and their expression increased further in the less drug-resistant cells, which had miR-23b knockout. This establishes that the balance of EMT contributes to the drug resistance, showing the importance of the miR-23b-mediated fine-tuning of EMT in oxaliplatin-resistant cancer cells.
Keywords: oxaliplatin; 5-fluorouracil; chemoresistance; microRNA; miRNome; proteome; epithelial–mesenchymal transition; drug resistance oxaliplatin; 5-fluorouracil; chemoresistance; microRNA; miRNome; proteome; epithelial–mesenchymal transition; drug resistance
MDPI and ACS Style

Gasiulė, S.; Dreize, N.; Kaupinis, A.; Ražanskas, R.; Čiupas, L.; Stankevičius, V.; Kapustina, Ž.; Laurinavičius, A.; Valius, M.; Vilkaitis, G. miR-23b Modulates the Epithelial–Mesenchymal Transition of Colorectal Cancer Cells. J. Clin. Med. 2019, 8, 2115.

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