Effects of imatinib and nilotinib on the whole transcriptome of cultured murine osteoblasts

Gyöngyi Kirschner, Bernadett Balla, P. Horváth, Andrea Kövesdi, Gergely Lakatos, I. Takács, Zsolt Nagy, Bálint Tóbiás, Kristóf Árvai, János Pál Kósa, P. Lakatos

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Numerous clinical observations have confirmed that breakpoint cluster region-abelson fusion oncoprotein tyrosine kinase inhibitors used in leukemia treatment alter bone physiology in a complex manner. The aim of the present study was to analyze the whole transcriptome of cultured murine osteoblasts and determine the changes following treatment with imatinib and nilotinib using Sequencing by Oligonucleotide Ligation and Detection next generation RNA sequencing. This study also aimed to identify candidate signaling pathways and network regulators by multivariate Ingenuity Pathway Analysis. Based on the right-tailed Fisher's exact test, significantly altered pathways including upstream regulators were defined for each drug. The correlation between these pathways and bone metabolism was also examined. The preliminary results suggest the two drugs have different mechanisms of action on osteoblasts, and imatinib was shown to have a greater effect on gene expression. Data also indicated the potential role of a number of genes and signaling cascades that may contribute to identifying novel targets for the treatment of metabolic bone diseases.

Original languageEnglish
Pages (from-to)2025-2037
Number of pages13
JournalMolecular Medicine Reports
Volume14
Issue number3
DOIs
Publication statusPublished - Sep 1 2016

Fingerprint

Osteoblasts
Transcriptome
Bone
RNA Sequence Analysis
Bone and Bones
Metabolic Bone Diseases
Oncogene Proteins
Gene Expression Profiling
Oligonucleotides
Pharmaceutical Preparations
Protein-Tyrosine Kinases
Ligation
Leukemia
Physiology
Gene Expression
Metabolism
Gene expression
Fusion reactions
Genes
RNA

Keywords

  • Gene expression
  • MC3T3-E1 cells
  • Pathway analysis
  • TKIs

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Oncology
  • Genetics
  • Cancer Research

Cite this

Effects of imatinib and nilotinib on the whole transcriptome of cultured murine osteoblasts. / Kirschner, Gyöngyi; Balla, Bernadett; Horváth, P.; Kövesdi, Andrea; Lakatos, Gergely; Takács, I.; Nagy, Zsolt; Tóbiás, Bálint; Árvai, Kristóf; Pál Kósa, János; Lakatos, P.

In: Molecular Medicine Reports, Vol. 14, No. 3, 01.09.2016, p. 2025-2037.

Research output: Contribution to journalArticle

Kirschner, G, Balla, B, Horváth, P, Kövesdi, A, Lakatos, G, Takács, I, Nagy, Z, Tóbiás, B, Árvai, K, Pál Kósa, J & Lakatos, P 2016, 'Effects of imatinib and nilotinib on the whole transcriptome of cultured murine osteoblasts', Molecular Medicine Reports, vol. 14, no. 3, pp. 2025-2037. https://doi.org/10.3892/mmr.2016.5459
Kirschner, Gyöngyi ; Balla, Bernadett ; Horváth, P. ; Kövesdi, Andrea ; Lakatos, Gergely ; Takács, I. ; Nagy, Zsolt ; Tóbiás, Bálint ; Árvai, Kristóf ; Pál Kósa, János ; Lakatos, P. / Effects of imatinib and nilotinib on the whole transcriptome of cultured murine osteoblasts. In: Molecular Medicine Reports. 2016 ; Vol. 14, No. 3. pp. 2025-2037.
@article{45819e9123ea48d1a43ef0d5e45bc57b,
title = "Effects of imatinib and nilotinib on the whole transcriptome of cultured murine osteoblasts",
abstract = "Numerous clinical observations have confirmed that breakpoint cluster region-abelson fusion oncoprotein tyrosine kinase inhibitors used in leukemia treatment alter bone physiology in a complex manner. The aim of the present study was to analyze the whole transcriptome of cultured murine osteoblasts and determine the changes following treatment with imatinib and nilotinib using Sequencing by Oligonucleotide Ligation and Detection next generation RNA sequencing. This study also aimed to identify candidate signaling pathways and network regulators by multivariate Ingenuity Pathway Analysis. Based on the right-tailed Fisher's exact test, significantly altered pathways including upstream regulators were defined for each drug. The correlation between these pathways and bone metabolism was also examined. The preliminary results suggest the two drugs have different mechanisms of action on osteoblasts, and imatinib was shown to have a greater effect on gene expression. Data also indicated the potential role of a number of genes and signaling cascades that may contribute to identifying novel targets for the treatment of metabolic bone diseases.",
keywords = "Gene expression, MC3T3-E1 cells, Pathway analysis, TKIs",
author = "Gy{\"o}ngyi Kirschner and Bernadett Balla and P. Horv{\'a}th and Andrea K{\"o}vesdi and Gergely Lakatos and I. Tak{\'a}cs and Zsolt Nagy and B{\'a}lint T{\'o}bi{\'a}s and Krist{\'o}f {\'A}rvai and {P{\'a}l K{\'o}sa}, J{\'a}nos and P. Lakatos",
year = "2016",
month = "9",
day = "1",
doi = "10.3892/mmr.2016.5459",
language = "English",
volume = "14",
pages = "2025--2037",
journal = "Molecular Medicine Reports",
issn = "1791-2997",
publisher = "Spandidos Publications",
number = "3",

}

TY - JOUR

T1 - Effects of imatinib and nilotinib on the whole transcriptome of cultured murine osteoblasts

AU - Kirschner, Gyöngyi

AU - Balla, Bernadett

AU - Horváth, P.

AU - Kövesdi, Andrea

AU - Lakatos, Gergely

AU - Takács, I.

AU - Nagy, Zsolt

AU - Tóbiás, Bálint

AU - Árvai, Kristóf

AU - Pál Kósa, János

AU - Lakatos, P.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Numerous clinical observations have confirmed that breakpoint cluster region-abelson fusion oncoprotein tyrosine kinase inhibitors used in leukemia treatment alter bone physiology in a complex manner. The aim of the present study was to analyze the whole transcriptome of cultured murine osteoblasts and determine the changes following treatment with imatinib and nilotinib using Sequencing by Oligonucleotide Ligation and Detection next generation RNA sequencing. This study also aimed to identify candidate signaling pathways and network regulators by multivariate Ingenuity Pathway Analysis. Based on the right-tailed Fisher's exact test, significantly altered pathways including upstream regulators were defined for each drug. The correlation between these pathways and bone metabolism was also examined. The preliminary results suggest the two drugs have different mechanisms of action on osteoblasts, and imatinib was shown to have a greater effect on gene expression. Data also indicated the potential role of a number of genes and signaling cascades that may contribute to identifying novel targets for the treatment of metabolic bone diseases.

AB - Numerous clinical observations have confirmed that breakpoint cluster region-abelson fusion oncoprotein tyrosine kinase inhibitors used in leukemia treatment alter bone physiology in a complex manner. The aim of the present study was to analyze the whole transcriptome of cultured murine osteoblasts and determine the changes following treatment with imatinib and nilotinib using Sequencing by Oligonucleotide Ligation and Detection next generation RNA sequencing. This study also aimed to identify candidate signaling pathways and network regulators by multivariate Ingenuity Pathway Analysis. Based on the right-tailed Fisher's exact test, significantly altered pathways including upstream regulators were defined for each drug. The correlation between these pathways and bone metabolism was also examined. The preliminary results suggest the two drugs have different mechanisms of action on osteoblasts, and imatinib was shown to have a greater effect on gene expression. Data also indicated the potential role of a number of genes and signaling cascades that may contribute to identifying novel targets for the treatment of metabolic bone diseases.

KW - Gene expression

KW - MC3T3-E1 cells

KW - Pathway analysis

KW - TKIs

UR - http://www.scopus.com/inward/record.url?scp=84989191913&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84989191913&partnerID=8YFLogxK

U2 - 10.3892/mmr.2016.5459

DO - 10.3892/mmr.2016.5459

M3 - Article

VL - 14

SP - 2025

EP - 2037

JO - Molecular Medicine Reports

JF - Molecular Medicine Reports

SN - 1791-2997

IS - 3

ER -