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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

(2020) CELLS. 9(5).
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Abstract
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.
Keywords
oncogenic miRNAs, acute lymphoblastic leukemia, silencing tumor suppressor genes, miRNA cluster, noncoding RNAs in cancer, ONCOGENIC PI3K, NETWORK, RNA, RISK, MYC, INACTIVATION, RESISTANCE, GENETICS, INSIGHTS, FEATURES

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MLA
Drobna, Monika, et al. “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, vol. 9, no. 5, 2020, doi:10.3390/cells9051137.
APA
Drobna, M., Szarzyńska, B., Jaksik, R., Sędek, Ł., Kuchmiy, A., Taghon, T., … Dawidowska, M. (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(5). https://doi.org/10.3390/cells9051137
Chicago author-date
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 (5). https://doi.org/10.3390/cells9051137.
Chicago author-date (all authors)
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 (5). doi:10.3390/cells9051137.
Vancouver
1.
Drobna M, Szarzyńska B, Jaksik R, Sędek Ł, Kuchmiy A, Taghon T, et al. 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).
IEEE
[1]
M. Drobna et al., “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, vol. 9, no. 5, 2020.
@article{8663523,
  abstract     = {{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.}},
  articleno    = {{1137}},
  author       = {{Drobna, Monika and Szarzyńska, Bronisława and Jaksik, Roman and Sędek, Łukasz and Kuchmiy, Anna and Taghon, Tom and Van Vlierberghe, Pieter and Szczepański, Tomasz and Witt, Michał and Dawidowska, Małgorzata}},
  issn         = {{2073-4409}},
  journal      = {{CELLS}},
  keywords     = {{oncogenic miRNAs,acute lymphoblastic leukemia,silencing tumor suppressor genes,miRNA cluster,noncoding RNAs in cancer,ONCOGENIC PI3K,NETWORK,RNA,RISK,MYC,INACTIVATION,RESISTANCE,GENETICS,INSIGHTS,FEATURES}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{19}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.3390/cells9051137}},
  volume       = {{9}},
  year         = {{2020}},
}

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