Etoposide-induced DNA damage affects multiple cellular pathways in addition to DNA damage response

Oncotarget
Fengxiang WeiDamu Tang

Abstract

DNA damage response (DDR) coordinates lesion repair and checkpoint activation. DDR is intimately connected with transcription. However, the relationship between DDR and transcription has not been clearly established. We report here RNA-sequencing analyses of MCF7 cells containing double-strand breaks induced by etoposide. While etoposide does not apparently cause global changes in mRNA abundance, it altered some gene expression. At the setting of fold alteration ≥ 2 and false discovery rate (FDR) ≤ 0.001, FDR < 0.05, or p < 0.05, etoposide upregulated 96, 268, or 860 genes and downregulated 41, 133, or 503 genes in MCF7 cells. Among these differentially expressed genes (DEGs), the processes of biogenesis, metabolism, cell motility, signal transduction, and others were affected; the pathways of Ras GTPase activity, RNA binding, cytokine-mediated signaling, kinase regulatory activity, protein binding, and translation were upregulated, and those pathways related to coated vesicle, calmodulin binding, and microtubule-based movement were downregulated. We further identified RABL6, RFTN2, FAS-AS1, and TCEB3CL as new DDR-affected genes in MCF7 and T47D cells. By metabolic labelling using 4-thiouridine, we observed dynamic alterations ...Continue Reading

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Datasets Mentioned

BETA
SRP104001

Methods Mentioned

BETA
GTPase
RNA-seq
PCR

Software Mentioned

Reactome
R
Reactome package
Gage
RSEM
GAGE package
Reactome package in
Bowtie2
Network map

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