RT Journal Article
SR Electronic
T1 Novel tumor suppressor roles for <em>GZMA</em> and <em>RASGRP1</em> in dissemination of both <em>Theileria annulata</em>-transformed macrophages and human B-lymphoma cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 338160
DO 10.1101/338160
A1 Zineb Rchiad
A1 Malak Haidar
A1 Hifzur Rahman Ansari
A1 Shahin Tajeri
A1 Sara Mfarrej
A1 Fathia Ben Rached
A1 Abhinav Kaushik
A1 Gordon Langsley
A1 Arnab Pain
YR 2019
UL http://biorxiv.org/content/early/2019/08/06/338160.abstract
AB Theileria annulata is a tick-transmitted apicomplexan parasite that infects and transforms bovine leukocytes into disseminating tumors that cause a disease called tropical theileriosis. Using comparative transcriptomics we identified genes transcriptionally perturbed during Theileria-induced 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 knock-down. Knocking down 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-lymphoma cells 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-lymphoma cells that overexpress GZMA and RASGRP1. Our results provide evidence that GZMA and RASGRP1 have a novel tumor suppressor function in both T. annulata-infected bovine host cells and in human B-lymphomas.Summary We compared the transcriptomes of Theileria annulata transformed B-lymphocytes to 934 human cancer cell lines and provide functional evidence for shared tumor suppressor roles for GZMA and RASGRP1 in controlling the dissemination phenotype of both human B lymphomas and Theileria-transformed leukocytes.