Characterisation of HIF-dependent alternative isoforms in pancreatic cancer

Intra-tumor hypoxia is a common feature in many solid cancers. Although transcriptional targets of hypoxia-inducible factors (HIFs) have been well characterized, alternative splicing or processing of pre-mRNA transcripts which occurs during hypoxia and subsequent HIF stabilization is much less understood. Here, we identify HIF-dependent alternative splicing events after whole transcriptome sequencing in pancreatic cancer cells exposed to hypoxia with and without downregulation of the aryl hydrocarbon receptor nuclear translocator (ARNT), a protein required for HIFs to form a transcriptionally active dimer. Overall design: We set out to perform whole transcriptome sequencing in pancreatic cancer cells with and without perturbation of HIF transcriptional activity (via siARNT) in normoxic (21% O2) and hypoxic (1% O2) settings. This results in 4 conditions, 3 replicates each.