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Article

hsa-miR-20b-5p and hsa-miR-363-3p Affect Expression of PTEN and BIM Tumor Suppressor Genes and Modulate Survival of T-ALL Cells In Vitro

1
Institute of Human Genetics Polish Academy of Sciences, 60-479 Poznań, Poland
2
Department of Systems Biology and Engineering, Silesian University of Technology, 44-100 Gliwice, Poland
3
Department of Microbiology and Immunology, Zabrze, Medical University of Silesia in Katowice, 41-808 Zabrze, Poland
4
Department of Diagnostic Sciences, Ghent University, 9000 Ghent, Belgium
5
Cancer Research Institute Ghent (CRIG), 9000 Ghent, Belgium
6
Department of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium
7
Department of Pediatric Hematology and Oncology, Zabrze, Medical University of Silesia in Katowice, 41-800 Zabrze, Poland
*
Author to whom correspondence should be addressed.
Currently: Polish Stem Cells Bank (PBKM), 00-867 Warsaw, Poland.
Cells 2020, 9(5), 1137; https://doi.org/10.3390/cells9051137
Received: 15 March 2020 / Revised: 30 April 2020 / Accepted: 1 May 2020 / Published: 5 May 2020
(This article belongs to the Special Issue Non-coding RNA in Cancer)
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy arising from T lymphocyte precursors. We have previously shown by miRNA-seq, that miRNAs from the mir-106a-363 cluster are overexpressed in pediatric T-ALL. In silico analysis indicated their potential involvement in the regulation of apoptosis. Here, we aimed to test the hypothesis on the pro-tumorigenic roles of these miRNAs in T-ALL cells in vitro. We demonstrate, for the first time, that hsa-miR-20b-5p and hsa-miR-363-3p from the mir-106a-363 cluster, when upregulated in T-ALL cells in vitro, protect leukemic cells from apoptosis, enhance proliferation, and contribute to growth advantage. We show, using dual luciferase reporter assays, Ago2-RNA immunoprecipitation, RT-qPCR, and Western blots, that the oncogenic effects of these upregulated miRNAs might, at least in part, be mediated by the downregulation of two important tumor suppressor genes, PTEN and BIM, targeted by both miRNAs. Additionally, we demonstrate the cooperative effects of these two miRNAs by simultaneous inhibition of both miRNAs as compared to the inhibition of single miRNAs. We postulate that hsa-miR-20b-5p and hsa-miR-363-3p from the mir-106a-363 cluster might serve as oncomiRs in T-ALL, by contributing to post-transcriptional repression of key tumor suppressors, PTEN and BIM. View Full-Text
Keywords: oncogenic miRNAs; acute lymphoblastic leukemia; silencing tumor suppressor genes; miRNA cluster; noncoding RNAs in cancer oncogenic miRNAs; acute lymphoblastic leukemia; silencing tumor suppressor genes; miRNA cluster; noncoding RNAs in cancer
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MDPI and ACS Style

Drobna, M.; Szarzyńska, B.; Jaksik, R.; Sędek, Ł.; Kuchmiy, A.; Taghon, T.; Van Vlierberghe, P.; Szczepański, T.; Witt, M.; Dawidowska, M. hsa-miR-20b-5p and hsa-miR-363-3p Affect Expression of PTEN and BIM Tumor Suppressor Genes and Modulate Survival of T-ALL Cells In Vitro. Cells 2020, 9, 1137. https://doi.org/10.3390/cells9051137

AMA Style

Drobna M, Szarzyńska B, Jaksik R, Sędek Ł, Kuchmiy A, Taghon T, Van Vlierberghe P, Szczepański T, Witt M, Dawidowska M. hsa-miR-20b-5p and hsa-miR-363-3p Affect Expression of PTEN and BIM Tumor Suppressor Genes and Modulate Survival of T-ALL Cells In Vitro. Cells. 2020; 9(5):1137. https://doi.org/10.3390/cells9051137

Chicago/Turabian Style

Drobna, Monika, Bronisława Szarzyńska, Roman Jaksik, Łukasz Sędek, Anna Kuchmiy, Tom Taghon, Pieter Van Vlierberghe, Tomasz Szczepański, Michał Witt, and Małgorzata Dawidowska. 2020. "hsa-miR-20b-5p and hsa-miR-363-3p Affect Expression of PTEN and BIM Tumor Suppressor Genes and Modulate Survival of T-ALL Cells In Vitro" Cells 9, no. 5: 1137. https://doi.org/10.3390/cells9051137

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