biostudies-literatureGuarnerio JU.S. Department of Health & Human Services | NIH | National Cancer InstituteNCI NIH HHSNovo Nordisk FondenNIH HHS628-640https://www.ebi.ac.uk/biostudies/studies/S-EPMC6796857biostudies-literatureUnknown29(8)circRNAs arise from back splicing events during mRNA processing, and when deregulated can play an active role in cancer. Here we characterize a new circRNA (circPOK) encoded by the Zbtb7a gene (also kown as POKEMON, LRF) in the context of mesenchymal tumor progression. circPOK functions as a non-coding proto-oncogenic RNA independently and antithetically to its linear transcript counterpart, which acts as a tumor suppressor by encoding the Pokemon transcription factor. We find that circPOK regulates pro-proliferative and pro-angiogenic factors by co-activation of the ILF2/3 complex. Importantly, the expression of Pokemon protein and circRNA is aberrantly uncoupled in cancer through differential post-transcriptional regulation. Thus, we identify a novel type of genetic unit, the iRegulon, tCell researchIntragenic antagonistic roles of protein and circRNA in tumorigenesis.PMC6796857R00 CA212200R35 CA197529DP5 OD012160NNF16SA0023584R01 CA178908K99 CA212200Kauppinen SNielsen GPPanella RMae Katon JCordon-Cardo CPandolfi PPPapa ABatish MDeshpande VMatsumoto APetri ADimitrios SZhang YCheloni GCastillo-Martin MLoretelli CGarbutt CSimpson MClohessy JGGuarnerio JfalseIntragenic antagonistic roles of protein and circRNA in tumorigenesis.circRNAs arise from back splicing events during mRNA processing, and when deregulated can play an active role in cancer. Here we characterize a new circRNA (circPOK) encoded by the Zbtb7a gene (also kown as POKEMON, LRF) in the context of mesenchymal tumor progression. circPOK functions as a non-coding proto-oncogenic RNA independently and antithetically to its linear transcript counterpart, which acts as a tumor suppressor by encoding the Pokemon transcription factor. We find that circPOK regulates pro-proliferative and pro-angiogenic factors by co-activation of the ILF2/3 complex. Importantly, the expression of Pokemon protein and circRNA is aberrantly uncoupled in cancer through differential post-transcriptional regulation. Thus, we identify a novel type of genetic unit, the iRegulon, t2019-01-01T00:00:00Z2019 Aug2025-04-19T04:30:57.636Z2025-04-19T04:30:57.636ZS-EPMC67968573120925010.1038/s41422-019-0192-1