Downregulation of both mismatch repair and non-homologous end-joining pathways in hypoxic brain tumour cell lines

Glioblastoma, a grade IV astrocytoma, has poor survival rate in part due to ineffective treatment options available. These tumours are heterogeneous with areas of low oxygen levels, termed hypoxic regions. Many intra-cellular signalling pathways, including DNA repair, can be altered by hypoxia. Since damage induction and subsequent activation repair mechanisms is the cornerstone glioblastoma treatment, alterations could have direct influence on success. Our aim was elucidate impact chronic hypoxia gene expression range cell lines. We adopted NanoString transcriptomic approach examine 180 repair-related genes four classical lines (U87-MG, U251-MG, D566-MG, T98G) exposed 5 days normoxia (21% O 2 ), moderate (1% ) or severe (0.1% observed several pathways homologous recombination non-homologous end-joining mismatch primarily resulting downregulation expression. The extent changes dependent severity. Some, but not all, these downregulations were directly under control HIF activity. For example, LIG4 , key component end-joining, reversed upon inhibition hypoxia-inducible factor (HIF). In contrast, gene, PMS2 affected inhibition. This suggests that numerous molecular lead hypoxia-induced reprogramming transcriptional landscape repair. Whilst global likely genomic instability, tumorigenesis reduced sensitivity anti-cancer re-sensitising might require additional approaches simple