The nuclear DICER-circular RNA complex drives the deregulation of the glioblastoma cell microRNAome.

Autor:	Bronisz A; Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. jgodlewski@bwh.harvard.edu abronisz@bwh.harvard.edu.; Department of Neurochemistry, Mossakowski Medical Research Centre of Polish Academy of Sciences, Warsaw, Poland., Rooj AK; Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Krawczyński K; Department of Neurochemistry, Mossakowski Medical Research Centre of Polish Academy of Sciences, Warsaw, Poland., Peruzzi P; Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Salińska E; Department of Neurochemistry, Mossakowski Medical Research Centre of Polish Academy of Sciences, Warsaw, Poland., Nakano I; Department of Neurosurgery, University of Alabama, Birmingham, AL, USA., Purow B; Department of Neurology, University of Virginia, Charlottesville, VA, USA., Chiocca EA; Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Godlewski J; Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. jgodlewski@bwh.harvard.edu abronisz@bwh.harvard.edu.; Department of Neurochemistry, Mossakowski Medical Research Centre of Polish Academy of Sciences, Warsaw, Poland.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2020 Dec 16; Vol. 6 (51). Date of Electronic Publication: 2020 Dec 16 (Print Publication: 2020).
DOI:	10.1126/sciadv.abc0221
Abstrakt:	The assortment of cellular microRNAs ("microRNAome") is a vital readout of cellular homeostasis, but the mechanisms that regulate the microRNAome are poorly understood. The microRNAome of glioblastoma is substantially down-regulated in comparison to the normal brain. Here, we find malfunction of the posttranscriptional maturation of the glioblastoma microRNAome and link it to aberrant nuclear localization of DICER, the major enzymatic complex responsible for microRNA maturation. Analysis of DICER's nuclear interactome reveals the presence of an RNA binding protein, RBM3, and of a circular RNA, circ2082 , within the complex. Targeting of this complex by knockdown of circ2082 results in the restoration of cytosolic localization of DICER and widespread derepression of the microRNAome, leading to transcriptome-wide rearrangements that mitigate the tumorigenicity of glioblastoma cells in vitro and in vivo with correlation to favorable outcomes in patients with glioblastoma. These findings uncover the mechanistic foundation of microRNAome deregulation in malignant cells. (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
Databáze:	MEDLINE
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