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Omics Technologies to Decipher Regulatory Networks in Granulocytic Cell Differentiation

Induced granulocytic differentiation of human leukemic cells under all-trans-retinoid acid (ATRA) treatment underlies differentiation therapy of acute myeloid leukemia. Knowing the regulation of this process it is possible to identify potential targets for antileukemic drugs and develop novel approa...

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Autores principales: Novikova, Svetlana, Tikhonova, Olga, Kurbatov, Leonid, Farafonova, Tatiana, Vakhrushev, Igor, Lupatov, Alexey, Yarygin, Konstantin, Zgoda, Victor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233756/
https://www.ncbi.nlm.nih.gov/pubmed/34207065
http://dx.doi.org/10.3390/biom11060907
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author Novikova, Svetlana
Tikhonova, Olga
Kurbatov, Leonid
Farafonova, Tatiana
Vakhrushev, Igor
Lupatov, Alexey
Yarygin, Konstantin
Zgoda, Victor
author_facet Novikova, Svetlana
Tikhonova, Olga
Kurbatov, Leonid
Farafonova, Tatiana
Vakhrushev, Igor
Lupatov, Alexey
Yarygin, Konstantin
Zgoda, Victor
author_sort Novikova, Svetlana
collection PubMed
description Induced granulocytic differentiation of human leukemic cells under all-trans-retinoid acid (ATRA) treatment underlies differentiation therapy of acute myeloid leukemia. Knowing the regulation of this process it is possible to identify potential targets for antileukemic drugs and develop novel approaches to differentiation therapy. In this study, we have performed transcriptomic and proteomic profiling to reveal up- and down-regulated transcripts and proteins during time-course experiments. Using data on differentially expressed transcripts and proteins we have applied upstream regulator search and obtained transcriptome- and proteome-based regulatory networks of induced granulocytic differentiation that cover both up-regulated (HIC1, NFKBIA, and CASP9) and down-regulated (PARP1, VDR, and RXRA) elements. To verify the designed network we measured HIC1 and PARP1 protein abundance during granulocytic differentiation by selected reaction monitoring (SRM) using stable isotopically labeled peptide standards. We also revealed that transcription factor CEBPB and LYN kinase were involved in differentiation onset, and evaluated their protein levels by SRM technique. Obtained results indicate that the omics data reflect involvement of the DNA repair system and the MAPK kinase cascade as well as show the balance between the processes of the cell survival and apoptosis in a p53-independent manner. The differentially expressed transcripts and proteins, predicted transcriptional factors, and key molecules such as HIC1, CEBPB, LYN, and PARP1 may be considered as potential targets for differentiation therapy of acute myeloid leukemia.
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spelling pubmed-82337562021-06-27 Omics Technologies to Decipher Regulatory Networks in Granulocytic Cell Differentiation Novikova, Svetlana Tikhonova, Olga Kurbatov, Leonid Farafonova, Tatiana Vakhrushev, Igor Lupatov, Alexey Yarygin, Konstantin Zgoda, Victor Biomolecules Article Induced granulocytic differentiation of human leukemic cells under all-trans-retinoid acid (ATRA) treatment underlies differentiation therapy of acute myeloid leukemia. Knowing the regulation of this process it is possible to identify potential targets for antileukemic drugs and develop novel approaches to differentiation therapy. In this study, we have performed transcriptomic and proteomic profiling to reveal up- and down-regulated transcripts and proteins during time-course experiments. Using data on differentially expressed transcripts and proteins we have applied upstream regulator search and obtained transcriptome- and proteome-based regulatory networks of induced granulocytic differentiation that cover both up-regulated (HIC1, NFKBIA, and CASP9) and down-regulated (PARP1, VDR, and RXRA) elements. To verify the designed network we measured HIC1 and PARP1 protein abundance during granulocytic differentiation by selected reaction monitoring (SRM) using stable isotopically labeled peptide standards. We also revealed that transcription factor CEBPB and LYN kinase were involved in differentiation onset, and evaluated their protein levels by SRM technique. Obtained results indicate that the omics data reflect involvement of the DNA repair system and the MAPK kinase cascade as well as show the balance between the processes of the cell survival and apoptosis in a p53-independent manner. The differentially expressed transcripts and proteins, predicted transcriptional factors, and key molecules such as HIC1, CEBPB, LYN, and PARP1 may be considered as potential targets for differentiation therapy of acute myeloid leukemia. MDPI 2021-06-18 /pmc/articles/PMC8233756/ /pubmed/34207065 http://dx.doi.org/10.3390/biom11060907 Text en © 2021 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
Novikova, Svetlana
Tikhonova, Olga
Kurbatov, Leonid
Farafonova, Tatiana
Vakhrushev, Igor
Lupatov, Alexey
Yarygin, Konstantin
Zgoda, Victor
Omics Technologies to Decipher Regulatory Networks in Granulocytic Cell Differentiation
title Omics Technologies to Decipher Regulatory Networks in Granulocytic Cell Differentiation
title_full Omics Technologies to Decipher Regulatory Networks in Granulocytic Cell Differentiation
title_fullStr Omics Technologies to Decipher Regulatory Networks in Granulocytic Cell Differentiation
title_full_unstemmed Omics Technologies to Decipher Regulatory Networks in Granulocytic Cell Differentiation
title_short Omics Technologies to Decipher Regulatory Networks in Granulocytic Cell Differentiation
title_sort omics technologies to decipher regulatory networks in granulocytic cell differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233756/
https://www.ncbi.nlm.nih.gov/pubmed/34207065
http://dx.doi.org/10.3390/biom11060907
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