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

‍Zineb Rchiad, Malak Haidar, Hifzur Rahman Ansari, Shahin Tajeri, Sara Mfarrej, Fathia Ben Rached, Abhinav Kaushik, Gordon Langsley, Arnab Pain

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5 Scopus citations

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.
Original languageEnglish (US)
JournalCellular Microbiology
DOIs
StatePublished - Aug 24 2020

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