Novel tumour suppressor roles for GZMA and RASGRP1 in Theileria annulata-transformed macrophages and human B-lymphoma cells
Type
ArticleAuthors
Rchiad, Zineb
Haidar, Malak
Ansari, Hifzur Rahman

Tajeri, Shahin
Mfarrej, Sara
Ben Rached, Fathia
Kaushik, Abhinav
Langsley, Gordon

Pain, Arnab

KAUST Department
Biological and Environmental Sciences and Engineering (BESE) DivisionBioscience Program
Computational Bioscience Research Center (CBRC)
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Pathogen Genomics Laboratory
Date
2020-09-29Online Publication Date
2020-09-29Print Publication Date
2020-12Embargo End Date
2021-08-24Submitted Date
2020-06-09Permanent link to this record
http://hdl.handle.net/10754/664809
Metadata
Show full item recordAbstract
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.13255Publisher
WileyJournal
Cellular MicrobiologyAdditional Links
https://onlinelibrary.wiley.com/doi/abs/10.1111/cmi.13255ae974a485f413a2113503eed53cd6c53
10.1111/cmi.13255