Cover Image: Novel tumour suppressor roles for GZMA and RASGRP1 in Theileria annulata-transformed macrophages and human B lymphoma cells (Cellular Microbiology 12/2020)

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

doi:10.1111/cmi.13285

Cover Image: Novel tumour suppressor roles for GZMA and RASGRP1 in Theileria annulata-transformed macrophages and human B lymphoma cells (Cellular Microbiology 12/2020)

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

Research output: Contribution to journal › Article › peer-review

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 language	English (US)
Journal	Cellular Microbiology
Volume	22
Issue number	12
DOIs	https://doi.org/10.1111/cmi.13285
State	Published - Nov 6 2020

Bibliographical note

KAUST Repository Item: Exported on 2020-11-10
Acknowledged KAUST grant number(s): OSR-2015-CRG4-2610
Acknowledgements: This study was supported by a Competitive Research Grant from the Office for Sponsored Research (OSR-2015-CRG4-2610) at King Abdullah University of Science and Technology (KAUST) awarded to A. P. and G. L. Z. R. acknowledges KAUST for awarding her PhD studentship. S. T. was supported by a post-doctoral fellowship from ParaFrap (ANR-11-LABX-0024) and in addition to ANR-11-LABX-0024, G. L. also acknowledges core support from INSERM and the CNRS. We thank members of the Bioscience Core Laboratory (BCL) at KAUST for producing the raw sequencing datasets. We also thank Franck Letourneur of the genomics platform at the Cochin Institute (GENOM'IC) for quantifying the pJET-ama-1 plasmid.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1111/cmi.13285

https://repository.kaust.edu.sa/bitstream/10754/665867/1/cmi.13255%20%281%29.pdf

Cite this

@article{485dec1a2c9d46c8adf91154a7270745,

title = "Cover Image: Novel tumour suppressor roles for GZMA and RASGRP1 in Theileria annulata-transformed macrophages and human B lymphoma cells (Cellular Microbiology 12/2020)",

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.",

author = "‍Zineb Rchiad and Malak Haidar and Ansari, {Hifzur Rahman} and Shahin Tajeri and Sara Mfarrej and {Ben Rached}, Fathia and Abhinav Kaushik and Gordon Langsley and Arnab Pain",

note = "KAUST Repository Item: Exported on 2020-11-10 Acknowledged KAUST grant number(s): OSR-2015-CRG4-2610 Acknowledgements: This study was supported by a Competitive Research Grant from the Office for Sponsored Research (OSR-2015-CRG4-2610) at King Abdullah University of Science and Technology (KAUST) awarded to A. P. and G. L. Z. R. acknowledges KAUST for awarding her PhD studentship. S. T. was supported by a post-doctoral fellowship from ParaFrap (ANR-11-LABX-0024) and in addition to ANR-11-LABX-0024, G. L. also acknowledges core support from INSERM and the CNRS. We thank members of the Bioscience Core Laboratory (BCL) at KAUST for producing the raw sequencing datasets. We also thank Franck Letourneur of the genomics platform at the Cochin Institute (GENOM'IC) for quantifying the pJET-ama-1 plasmid.",

year = "2020",

month = nov,

day = "6",

doi = "10.1111/cmi.13285",

language = "English (US)",

volume = "22",

journal = "Cellular Microbiology",

issn = "1462-5814",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "12",

}

TY - JOUR

T1 - Cover Image: Novel tumour suppressor roles for GZMA and RASGRP1 in Theileria annulata-transformed macrophages and human B lymphoma cells (Cellular Microbiology 12/2020)

AU - Rchiad, ‍Zineb

AU - Haidar, Malak

AU - Ansari, Hifzur Rahman

AU - Tajeri, Shahin

AU - Mfarrej, Sara

AU - Ben Rached, Fathia

AU - Kaushik, Abhinav

AU - Langsley, Gordon

AU - Pain, Arnab

N1 - KAUST Repository Item: Exported on 2020-11-10 Acknowledged KAUST grant number(s): OSR-2015-CRG4-2610 Acknowledgements: This study was supported by a Competitive Research Grant from the Office for Sponsored Research (OSR-2015-CRG4-2610) at King Abdullah University of Science and Technology (KAUST) awarded to A. P. and G. L. Z. R. acknowledges KAUST for awarding her PhD studentship. S. T. was supported by a post-doctoral fellowship from ParaFrap (ANR-11-LABX-0024) and in addition to ANR-11-LABX-0024, G. L. also acknowledges core support from INSERM and the CNRS. We thank members of the Bioscience Core Laboratory (BCL) at KAUST for producing the raw sequencing datasets. We also thank Franck Letourneur of the genomics platform at the Cochin Institute (GENOM'IC) for quantifying the pJET-ama-1 plasmid.

PY - 2020/11/6

Y1 - 2020/11/6

N2 - 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.

AB - 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.

UR - http://hdl.handle.net/10754/665867

UR - https://onlinelibrary.wiley.com/doi/10.1111/cmi.13285

U2 - 10.1111/cmi.13285

DO - 10.1111/cmi.13285

M3 - Article

SN - 1462-5814

VL - 22

JO - Cellular Microbiology

JF - Cellular Microbiology

IS - 12

ER -

Cover Image: Novel tumour suppressor roles for GZMA and RASGRP1 in Theileria annulata-transformed macrophages and human B lymphoma cells (Cellular Microbiology 12/2020)

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this