Transcriptomic profiling of gamma ray induced mutants from the CGL1 human hybrid cell system reveals novel insights into the mechanisms of radiation-induced carcinogenesis.
Carcinogenesis
/ genetics
Fibroblasts
/ metabolism
Gamma Rays
/ adverse effects
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
/ radiation effects
HeLa Cells
Humans
Hybrid Cells
/ radiation effects
Mutation
/ radiation effects
Neoplasm Proteins
/ genetics
Neoplasms, Radiation-Induced
/ genetics
Transcriptome
/ radiation effects
CGL1 cells
Cancer
Carcinogenesis
Fibroblast
Gene expression profiling
HeLa
Hybrid cells
Microarray
Radiation
Transcriptomics
Tumorigenesis
Journal
Free radical biology & medicine
ISSN: 1873-4596
Titre abrégé: Free Radic Biol Med
Pays: United States
ID NLM: 8709159
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
15
03
2019
revised:
22
08
2019
accepted:
29
09
2019
pubmed:
4
10
2019
medline:
4
9
2020
entrez:
4
10
2019
Statut:
ppublish
Résumé
Somatic cell hybrid systems generated by combining cancerous with non-cancerous cells provide useful model systems to study neoplastic transformation. Combined with recent advances in omics-based technologies, novel molecular signatures that drive radiation-induced carcinogenesis can be analyzed at an exceptional global level. Here, we present a complete whole-transcriptome analysis of gamma-induced mutants (GIM) and gamma irradiated control (CON) segregants isolated from the CGL1 (HeLa x normal fibroblast) human hybrid cell-system exposed to high doses of radiation. Using the Human Transcriptome Array 2.0 microarray technology and conservative discrimination parameters, we have elucidated 1067 differentially expressed genes (DEGs) between tumorigenic and non-tumorigenic cells. Gene ontology enrichment analysis revealed that tumorigenic cells demonstrated shifts in extracellular matrix (ECM) and cellular adhesion profiles, dysregulation of cyclic AMP (cAMP) signaling, and alterations in nutrient transport and cellular energetics. Furthermore, putative upstream master regulator analysis demonstrated that loss of TGFβ1 signaling due to reduced SMAD3 expression is involved in radiation-induced carcinogenesis. Taken together, this study presents novel insights into specific gene expression and pathway level differences that contribute to radiation-induced carcinogenesis in a human cell-based model. This global transcriptomic analysis and our published tumor suppressor gene deletion loci analyses will allow us to identify and functionally test candidate nexus upstream tumor suppressor genes that are deleted or silenced after exposure to radiation.
Sections du résumé
BACKGROUND
Somatic cell hybrid systems generated by combining cancerous with non-cancerous cells provide useful model systems to study neoplastic transformation. Combined with recent advances in omics-based technologies, novel molecular signatures that drive radiation-induced carcinogenesis can be analyzed at an exceptional global level.
METHODS
Here, we present a complete whole-transcriptome analysis of gamma-induced mutants (GIM) and gamma irradiated control (CON) segregants isolated from the CGL1 (HeLa x normal fibroblast) human hybrid cell-system exposed to high doses of radiation. Using the Human Transcriptome Array 2.0 microarray technology and conservative discrimination parameters, we have elucidated 1067 differentially expressed genes (DEGs) between tumorigenic and non-tumorigenic cells.
RESULTS
Gene ontology enrichment analysis revealed that tumorigenic cells demonstrated shifts in extracellular matrix (ECM) and cellular adhesion profiles, dysregulation of cyclic AMP (cAMP) signaling, and alterations in nutrient transport and cellular energetics. Furthermore, putative upstream master regulator analysis demonstrated that loss of TGFβ1 signaling due to reduced SMAD3 expression is involved in radiation-induced carcinogenesis.
CONCLUSIONS
Taken together, this study presents novel insights into specific gene expression and pathway level differences that contribute to radiation-induced carcinogenesis in a human cell-based model. This global transcriptomic analysis and our published tumor suppressor gene deletion loci analyses will allow us to identify and functionally test candidate nexus upstream tumor suppressor genes that are deleted or silenced after exposure to radiation.
Identifiants
pubmed: 31580949
pii: S0891-5849(19)30451-4
doi: 10.1016/j.freeradbiomed.2019.09.037
pii:
doi:
Substances chimiques
Neoplasm Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
300-311Subventions
Organisme : NCI NIH HHS
ID : R01 CA090885
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.