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3篇 您的检索式:作者名="Giulia Cheloni"
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1Intragenic antagonistic roles of protein and circRNA in tumorigenesis显示文摘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.Jlenia Guarnerio Yang Zhang Giulia Cheloni Riccardo Panella Jesse Mae Katon Mark Simpson Akinobu Matsumoto Antonella Papa Cristian Loretelli Andreas Petri Sakari Kauppinen Cassandra Garbutt Gunnlaugur Petur Nielsen Vikram Deshpande Mireia Castillo-Martin Carlos Cordon-Cardo Spentzos Dimitrios John G. Clohessy Mona Batish Pier Paolo Pandolfi 2019Cell Research2019,29,8:15
2Vulnerabilities in mIDH2 AML confer sensitivity to APL-like targeted combination therapy显示文摘Although targeted therapies have proven effective and even curative in human leukaemia, resistance often ensues. IDH enzymes are mutated in ~20% of human AML, with targeted therapies under clinical evaluation. We here characterize leukaemia evolution from mutant IDH2 (mIDH2)-dependence to independence identifying key targetable vulnerabilities of mIDH2 leukaemia that are retained during evolution and progression from early to late stages. Mechanistically, we find that mIDH2 leukaemia are metastable and vulnerable at two distinct levels. On the one hand, they are characterized by oxidative and genotoxic stress, in spite of increased 1-carbon metabolism and glutathione levels. On the other hand, mIDH2 leukaemia display inhibition of LSD1 and a resulting transcriptional signature of all-trans retinoic acid (ATRA) sensitization, in spite of a state of suppressed ATRA signalling due to increased levels of PIN1. We further identify GSH/ROS and PIN1/LSD1 as critical nodes for leukaemia maintenance and the combination of ATRA and arsenic trioxide (ATO) as a key therapeutic modality to target these vulnerabilities. Strikingly, we demonstrate that the combination of ATRA and ATO proves to be a powerfully synergistic and effective therapy in a number of mouse and human mIDH1/2 leukemic models. Thus, our findings pave the way towards the treatment of a sizable fraction of human AMLs through targeted APL-like combinatorial therapies.Vera Mugoni Riccardo Panella Giulia Cheloni Ming Chen Olga Pozdnyakova Dina Stroopinsky Jlenia Guarnerio Emanuele Monteleone Jonathan David Lee Lourdes Mendez Archita Venugopal Menon Jon Christopher Aster Andrew A. Lane Richard Maury Stone Ilene Galinsky José Cervera Zamora Francesco Lo-Coco Manoj Kumar Bhasin David Avigan Letizia Longo John Gerard Clohessy Pier Paolo Pandolfi 2019Cell Research2019,29,6:1
3Author Correction:Intragenic antagonistic roles of protein and circ RNA in tumorigenesis显示文摘We apologize for author name and affiliation errors that we just identified in our paper published in 2019 August issue.There were mistakes in the name of one author and the location of institutional affiliations for four authors.Specifically,author'D im itrios Spentzos'was previously listed as'Spentzos Dim itrios'resulting in a reversal of his first and last nam e.Jlenia Guarnerio Yang Zhang Giulia Cheloni Riccardo Panella Jesse Mae Katon Mark Simpson Akinobu Matsumoto Antonella Papa Cristian Loretelli Andreas Petri Sakari Kauppinen Cassandra Garbutt Gunnlaugur Petur Nielsen Vikram Deshpande Mireia Castillo-Martin Carlos Cordon-Cardo Dimitrios Spentzos John G.Clohessy Mona Batish Pier Paolo Pandolfi 2020Cell Research2020,30,2:0
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