GZMA and RASGRP1 are novel tumor suppressors that counter dissemination of Theileria annulata-transformed macrophages
Ansari, Hifzur Rahman
Ben Rached, Fathia
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Computational Bioscience Research Center (CBRC)
Pathogen Genomics Laboratory
KAUST Grant NumberOSR-2015-CRG4-2610
Permanent link to this recordhttp://hdl.handle.net/10754/628453
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AbstractTheileria annulata is a tick-transmitted apicomplexan parasite that infects and transforms bovine leukocytes into disseminating tumors that cause a disease called tropical theileriosis. Using RNA sequencing we identified bovine genes, whose transcription is perturbed during Theileria-induced transformation to define the transcriptional atlas of transformed virulent versus attenuated (dampened dissemination) macrophages and transformed B cells. Dataset comparisons highlighted a small set of novel genes associated with Theileria-transformed leukocyte dissemination and the roles of Granzyme A (GZMA) and RAS guanyl-releasing protein 1 (RASGRP1) confirmed by CRISPR/Cas9-mediated down-regulation of their expression. Knockdown of both GZMA and RASGRP1 in attenuated macrophages led to a regain in their dissemination in Rag2/γC mice confirming in vivo both GZMA and RASGRP1 as novel dissemination suppressors.
CitationRchiad Z, Haidar M, Ansari HR, Tajeri S, Ben Rached F, et al. (2018) GZMA and RASGRP1 are novel tumor suppressors that counter dissemination of Theileria annulata-transformed macrophages. Available: http://dx.doi.org/10.1101/338160.
SponsorsThis study was supported by the Competitive Research Grant 4 (OSR-2015-CRG4-2610) from the Office for Sponsored Research in King Abdullah University of Science and Technology (KAUST). ST was supported by a ParaFrap postdoctoral fellowship and GL acknowledges support from Labex ParaFrap (ANR-11-LABX-0024), INSERM and the CNRS.
PublisherCold Spring Harbor Laboratory
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