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Small RNA-Seq Reveals Similar miRNA Transcriptome in Children and Young Adults with T-ALL and Indicates miR-143-3p as Novel Candidate Tumor Suppressor in This Leukemia

We aimed to identify miRNAs and pathways specifically deregulated in adolescent and young adult (AYA) T-ALL patients. Small RNA-seq showed no major differences between AYA and pediatric T-ALL, but it revealed downregulation of miR-143-3p in T-ALL patients. Prediction algorithms identified several kn...

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Autores principales: Dawidowska, Małgorzata, Maćkowska-Maślak, Natalia, Drobna-Śledzińska, Monika, Kosmalska, Maria, Jaksik, Roman, Szymczak, Donata, Jarmuż-Szymczak, Małgorzata, Sadowska-Klasa, Alicja, Wojtaszewska, Marzena, Sędek, Łukasz, Wróbel, Tomasz, Zaucha, Jan Maciej, Szczepański, Tomasz, Lewandowski, Krzysztof, Giebel, Sebastian, Witt, Michał
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456032/
https://www.ncbi.nlm.nih.gov/pubmed/36077521
http://dx.doi.org/10.3390/ijms231710117
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author Dawidowska, Małgorzata
Maćkowska-Maślak, Natalia
Drobna-Śledzińska, Monika
Kosmalska, Maria
Jaksik, Roman
Szymczak, Donata
Jarmuż-Szymczak, Małgorzata
Sadowska-Klasa, Alicja
Wojtaszewska, Marzena
Sędek, Łukasz
Wróbel, Tomasz
Zaucha, Jan Maciej
Szczepański, Tomasz
Lewandowski, Krzysztof
Giebel, Sebastian
Witt, Michał
author_facet Dawidowska, Małgorzata
Maćkowska-Maślak, Natalia
Drobna-Śledzińska, Monika
Kosmalska, Maria
Jaksik, Roman
Szymczak, Donata
Jarmuż-Szymczak, Małgorzata
Sadowska-Klasa, Alicja
Wojtaszewska, Marzena
Sędek, Łukasz
Wróbel, Tomasz
Zaucha, Jan Maciej
Szczepański, Tomasz
Lewandowski, Krzysztof
Giebel, Sebastian
Witt, Michał
author_sort Dawidowska, Małgorzata
collection PubMed
description We aimed to identify miRNAs and pathways specifically deregulated in adolescent and young adult (AYA) T-ALL patients. Small RNA-seq showed no major differences between AYA and pediatric T-ALL, but it revealed downregulation of miR-143-3p in T-ALL patients. Prediction algorithms identified several known and putative oncogenes targeted by this miRNA, including KRAS, FGF1, and FGF9. Pathway analysis indicated signaling pathways related to cell growth and proliferation, including FGFR signaling and PI3K-AKT signaling, with the majority of genes overrepresented in these pathways being predicted targets of hsa-miR-143-3p. By luciferase reporter assays, we validated direct interactions of this miRNA with KRAS, FGF1 and FGF9. In cell proliferation assays, we showed reduction of cell growth upon miR-143-3p overexpression in two T-ALL cell lines. Our study is the first description of the miRNA transcriptome in AYA T-ALL patients and the first report on tumor suppressor potential of miR-143-3p in T-ALL. Downregulation of this miRNA in T-ALL patients might contribute to enhanced growth and viability of leukemic cells. We also discuss the potential role of miR-143-3p in FGFR signaling. Although this requires more extensive validation, it might be an interesting direction, since FGFR inhibition proved promising in preclinical studies in various cancers.
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spelling pubmed-94560322022-09-09 Small RNA-Seq Reveals Similar miRNA Transcriptome in Children and Young Adults with T-ALL and Indicates miR-143-3p as Novel Candidate Tumor Suppressor in This Leukemia Dawidowska, Małgorzata Maćkowska-Maślak, Natalia Drobna-Śledzińska, Monika Kosmalska, Maria Jaksik, Roman Szymczak, Donata Jarmuż-Szymczak, Małgorzata Sadowska-Klasa, Alicja Wojtaszewska, Marzena Sędek, Łukasz Wróbel, Tomasz Zaucha, Jan Maciej Szczepański, Tomasz Lewandowski, Krzysztof Giebel, Sebastian Witt, Michał Int J Mol Sci Article We aimed to identify miRNAs and pathways specifically deregulated in adolescent and young adult (AYA) T-ALL patients. Small RNA-seq showed no major differences between AYA and pediatric T-ALL, but it revealed downregulation of miR-143-3p in T-ALL patients. Prediction algorithms identified several known and putative oncogenes targeted by this miRNA, including KRAS, FGF1, and FGF9. Pathway analysis indicated signaling pathways related to cell growth and proliferation, including FGFR signaling and PI3K-AKT signaling, with the majority of genes overrepresented in these pathways being predicted targets of hsa-miR-143-3p. By luciferase reporter assays, we validated direct interactions of this miRNA with KRAS, FGF1 and FGF9. In cell proliferation assays, we showed reduction of cell growth upon miR-143-3p overexpression in two T-ALL cell lines. Our study is the first description of the miRNA transcriptome in AYA T-ALL patients and the first report on tumor suppressor potential of miR-143-3p in T-ALL. Downregulation of this miRNA in T-ALL patients might contribute to enhanced growth and viability of leukemic cells. We also discuss the potential role of miR-143-3p in FGFR signaling. Although this requires more extensive validation, it might be an interesting direction, since FGFR inhibition proved promising in preclinical studies in various cancers. MDPI 2022-09-04 /pmc/articles/PMC9456032/ /pubmed/36077521 http://dx.doi.org/10.3390/ijms231710117 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Dawidowska, Małgorzata
Maćkowska-Maślak, Natalia
Drobna-Śledzińska, Monika
Kosmalska, Maria
Jaksik, Roman
Szymczak, Donata
Jarmuż-Szymczak, Małgorzata
Sadowska-Klasa, Alicja
Wojtaszewska, Marzena
Sędek, Łukasz
Wróbel, Tomasz
Zaucha, Jan Maciej
Szczepański, Tomasz
Lewandowski, Krzysztof
Giebel, Sebastian
Witt, Michał
Small RNA-Seq Reveals Similar miRNA Transcriptome in Children and Young Adults with T-ALL and Indicates miR-143-3p as Novel Candidate Tumor Suppressor in This Leukemia
title Small RNA-Seq Reveals Similar miRNA Transcriptome in Children and Young Adults with T-ALL and Indicates miR-143-3p as Novel Candidate Tumor Suppressor in This Leukemia
title_full Small RNA-Seq Reveals Similar miRNA Transcriptome in Children and Young Adults with T-ALL and Indicates miR-143-3p as Novel Candidate Tumor Suppressor in This Leukemia
title_fullStr Small RNA-Seq Reveals Similar miRNA Transcriptome in Children and Young Adults with T-ALL and Indicates miR-143-3p as Novel Candidate Tumor Suppressor in This Leukemia
title_full_unstemmed Small RNA-Seq Reveals Similar miRNA Transcriptome in Children and Young Adults with T-ALL and Indicates miR-143-3p as Novel Candidate Tumor Suppressor in This Leukemia
title_short Small RNA-Seq Reveals Similar miRNA Transcriptome in Children and Young Adults with T-ALL and Indicates miR-143-3p as Novel Candidate Tumor Suppressor in This Leukemia
title_sort small rna-seq reveals similar mirna transcriptome in children and young adults with t-all and indicates mir-143-3p as novel candidate tumor suppressor in this leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456032/
https://www.ncbi.nlm.nih.gov/pubmed/36077521
http://dx.doi.org/10.3390/ijms231710117
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