GSE128798 Chemotherapeutic drugs inhibiting Topoisomerase 1 activity inhibit TNF-induced inflammatory gene expression

Contributors : Lienhard M Schmitz ; Marek Bartkuhn ; Tabea Riedlinger ; Tobias ZimmermannSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensInhibitors of DNA topoisomerase I (TOP1), an enzyme relieving torsional stress of DNA by generating transient single-strand breaks, are clinically used to treat ovarian cancer, small cell lung cancer and cervical cancer. As torsional stress is generated by replication and transcription we tested the effects of clinically used TOP1 inhibitors Topotecan and SN-38 on TNF-induced gene expression. RNA-seq experiments showed that inhibition of TOP1 activity interfered with the vast majority of TNF-triggered genes, while interference with TOP2 activity had only a minor impact. TOP1 inhibition affected the expression of early and late induced genes and the relative strength of gene induction played no role in the sensitivity to TOP1 interfering drugs. These data raise the possibility that the inhibition of inflammatory gene expression contributes to the increased risk of infection seen in some patients treated with TOP1 inhibtors.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research