Novel tumour suppressor roles forGZMAandRASGRP1inTheileria annulata-transformed macrophages and human B lymphoma cells


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Output type: Journal article

UM6P affiliated Publication?: Yes

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

Publisher: Wiley: 12 months

Publication year: 2020

Journal: Cellular Microbiology (1462-5814)

Volume number: 22

Issue number: 12

ISSN: 1462-5814

eISSN: 1462-5822

Languages: English (EN-GB)


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Abstract

Theileria annulatais 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 duringTheileria-induced leukocyte transformation. Dataset comparisons highlighted a small set of genes associated withTheileria-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 ofGZMAandRASGRP1in attenuated macrophages led to a regain in their dissemination in Rag2/gamma C mice confirming their role as dissemination suppressors in vivo. We further evaluated the roles ofGZMAandRASGRP1in human B lymphomas by comparing the transcriptome of 934 human cancer cell lines to that ofTheileria-transformed bovine host cells. We confirmed dampened dissemination potential of human B lymphomas that overexpressGZMAandRASGRP1. Our results provide evidence thatGZMAandRASGRP1have a novel tumour suppressor function in bothT. annulata-infected bovine host leukocytes and in human B lymphomas.


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Last updated on 2021-04-04 at 23:20