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    Novel tumour suppressor roles for GZMA and RASGRP1 in Theileria annulata-transformed macrophages and human B-lymphoma cells

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    cmi.13255.pdf
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    Description:
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    Type
    Article
    Authors
    Rchiad, ‍Zineb cc
    Haidar, Malak
    Ansari, Hifzur Rahman cc
    Tajeri, Shahin
    Mfarrej, Sara
    Ben Rached, Fathia
    Kaushik, Abhinav
    Langsley, Gordon cc
    Pain, Arnab cc
    KAUST Department
    Biological and Environmental Sciences and Engineering (BESE) Division
    Bioscience Program
    Computational Bioscience Research Center (CBRC)
    Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
    Pathogen Genomics Laboratory
    Date
    2020-09-29
    Online Publication Date
    2020-09-29
    Print Publication Date
    2020-12
    Embargo End Date
    2021-08-24
    Submitted Date
    2020-06-09
    Permanent link to this record
    http://hdl.handle.net/10754/664809
    
    Metadata
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    Abstract
    Theileria annulata is a tick-transmitted apicomplexan parasite that infects and transforms bovine leukocytes into disseminating tumours that cause a disease called tropical theileriosis. Using comparative transcriptomics we identified genes transcriptionally perturbed during Theileria-induced leukocyte transformation. Dataset comparisons highlighted a small set of genes associated with Theileria-transformed leukocyte dissemination. The roles of Granzyme A (GZMA) and RAS guanyl-releasing protein 1 (RASGRP1) were verified by CRISPR/Cas9-mediated knockdown. Knocking down expression of GZMA and RASGRP1 in attenuated macrophages led to a regain in their dissemination in Rag2/γC mice confirming their role as dissemination suppressors in vivo. We further evaluated the roles of GZMA and RASGRP1 in human B-lymphomas by comparing the transcriptome of 934 human cancer cell lines to that of Theileria-transformed bovine host cells. We confirmed dampened dissemination potential of human B-lymphomas that overexpress GZMA and RASGRP1. Our results provide evidence that GZMA and RASGRP1 have a novel tumour suppressor function in both T. annulata-infected bovine host leukocytes and in human B-lymphomas.
    Citation
    Rchiad, Z., Haidar, M., Ansari, H. R., Tajeri, S., Mfarrej, S., Ben Rached, F., … Pain, A. (2020). Novel tumour suppressor roles for GZMA and RASGRP1 in Theileria annulata -transformed macrophages and human B-lymphoma cells. Cellular Microbiology. doi:10.1111/cmi.13255
    Publisher
    Wiley
    Journal
    Cellular Microbiology
    DOI
    10.1111/cmi.13255
    Additional Links
    https://onlinelibrary.wiley.com/doi/abs/10.1111/cmi.13255
    ae974a485f413a2113503eed53cd6c53
    10.1111/cmi.13255
    Scopus Count
    Collections
    Articles; Biological and Environmental Science and Engineering (BESE) Division; Bioscience Program; Computational Bioscience Research Center (CBRC); Computer, Electrical and Mathematical Science and Engineering (CEMSE) Division

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