Genome-scale CRISPR-Cas9 knockout screening in gastrointestinal stromal tumor with Imatinib resistance

Jie Cao; Jianchang Wei; Ping Yang; Tong Zhang; Zhuanpeng Chen; Feng He; Fang Wei; Huacui Chen; He Hu; Junbin Zhong; Zhi Yang; Wensong Cai; Wanglin Li; Qiang Wang

doi:10.1186/s12943-018-0865-2

Molecular Cancer (Aug 2018)

Genome-scale CRISPR-Cas9 knockout screening in gastrointestinal stromal tumor with Imatinib resistance

Jie Cao,
Jianchang Wei,
Ping Yang,
Tong Zhang,
Zhuanpeng Chen,
Feng He,
Fang Wei,
Huacui Chen,
He Hu,
Junbin Zhong,
Zhi Yang,
Wensong Cai,
Wanglin Li,
Qiang Wang

Affiliations

Jie Cao: Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, Guangzhou Medical University, the Second Affiliated Hospital of South China University of Technology
Jianchang Wei: Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, Guangzhou Medical University, the Second Affiliated Hospital of South China University of Technology
Ping Yang: Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, Guangzhou Medical University, the Second Affiliated Hospital of South China University of Technology
Tong Zhang: Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, Guangzhou Medical University, the Second Affiliated Hospital of South China University of Technology
Zhuanpeng Chen: Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, Guangzhou Medical University, the Second Affiliated Hospital of South China University of Technology
Feng He: Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, Guangzhou Medical University, the Second Affiliated Hospital of South China University of Technology
Fang Wei: Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, Guangzhou Medical University, the Second Affiliated Hospital of South China University of Technology
Huacui Chen: Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, Guangzhou Medical University, the Second Affiliated Hospital of South China University of Technology
He Hu: Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, Guangzhou Medical University, the Second Affiliated Hospital of South China University of Technology
Junbin Zhong: Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, Guangzhou Medical University, the Second Affiliated Hospital of South China University of Technology
Zhi Yang: Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, Guangzhou Medical University, the Second Affiliated Hospital of South China University of Technology
Wensong Cai: Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, Guangzhou Medical University, the Second Affiliated Hospital of South China University of Technology
Wanglin Li: Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, Guangzhou Medical University, the Second Affiliated Hospital of South China University of Technology
Qiang Wang: Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, Guangzhou Medical University, the Second Affiliated Hospital of South China University of Technology

DOI: https://doi.org/10.1186/s12943-018-0865-2
Journal volume & issue: Vol. 17, no. 1
pp. 1 – 6

Abstract

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Abstract Genome-scale CRISPR-Cas9 Knockout Screening was applied to investigate novel targets in imatinib-resistant gastrointestinal stromal tumor (GIST). 20 genes and 2 miRNAs have been selected by total reads of sgRNA and sgRNA diversity, which has been further validated in imatinib-resistant GIST cells by CCK8 and qPCR analysis. Our study has finally revealed 9 genes (DBP, NR3C1, TCF12, TP53, ZNF12, SOCS6, ZFP36, ACYP1, and DRD1) involved in imatinib-resistant GIST-T1 cells. TP53 and SOCS6 may be the most promising candidate genes for imatinib-resistance due to the possible signaling pathway, such as apoptosis pathway and Wnt signaling pathway, JAK-STAT signaling pathway. It is necessary to perform more studies to discover novel targets in imatinib-resistant GIST, including DBP, NR3C1, TCF12, ZNF12, ZFP36, ACYP1 and DRD1.

Published in Molecular Cancer

ISSN: 1476-4598 (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://molecular-cancer.biomedcentral.com/

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Abstract

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