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, that yields biochemically distinct RNA products, circular and linear, with diverse and antithetical functions. Our findings further expand the cellular repertoire towards the control of normal biological outputs, while aberrant expression of such components may underlie disease pathogenesis including cancer.
Intragenic antagonistic roles of protein and circRNA in tumorigenesis / J. Guarnerio, Y. Zhang, G. Cheloni, R. Panella, J. Mae Katon, M. Simpson, A. Matsumoto, A. Papa, C. Loretelli, A. Petri, S. Kauppinen, C. Garbutt, G. Petur Nielsen, V. Deshpande, M. Castillo-Martin, C. Cordon-Cardo, S. Dimitrios, J.G. Clohessy, M. Batish, P.P. Pandolfi. - In: CELL RESEARCH. - ISSN 1001-0602. - 29:8(2019 Aug), pp. 628-640.
|Titolo:||Intragenic antagonistic roles of protein and circRNA in tumorigenesis|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
Settore MED/03 - Genetica Medica
Settore MED/06 - Oncologia Medica
Settore BIO/13 - Biologia Applicata
|Data di pubblicazione:||ago-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/s41422-019-0192-1|
|Appare nelle tipologie:||01 - Articolo su periodico|
File in questo prodotto:
|Intragenic antagonistic roles of protein and circRNA in tumorigenesis.pdf||Publisher's version/PDF||Open Access Visualizza/Apri|