@article {Markolin826156, author = {Philipp Markolin and Natalie Davidson and Christian K. Hirt and Christophe D. Chabbert and Nicola Zamboni and Gerald Schwank and Wilhelm Krek and Gunnar R{\"a}tsch}, title = {Characterisation of HIF-dependent alternative isoforms in pancreatic cancer}, elocation-id = {826156}, year = {2020}, doi = {10.1101/826156}, publisher = {Cold Spring Harbor Laboratory}, abstract = {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. We correlate the discovered hypoxia-driven events with available sequencing data from pan-cancer TCGA patient cohorts to select a narrow set of putative biologically relevant splice events for experimental validation. We validate a small set of candidate HIF-dependent alternative splicing events in multiple human cancer cell lines as well as patient-derived human pancreatic cancer organoids. Lastly, we report the discovery of a HIF-dependent mechanism to produce a hypoxia-dependent, long and coding isoform of the UDP-N-acetylglucosamine transporter SLC35A3.}, URL = {https://www.biorxiv.org/content/early/2020/02/14/826156}, eprint = {https://www.biorxiv.org/content/early/2020/02/14/826156.full.pdf}, journal = {bioRxiv} }