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Molecular Cancer
Published in: Molecular Cancer 1/2018

Open Access 01-12-2018 | Letter to the Editor

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

Authors: 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

Published in: Molecular Cancer | Issue 1/2018

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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.
Appendix
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Literature
1.
Lai S, Wang G, Cao X, Luo X, Wang G, Xia X, Hu J, Wang J. KIT over-expression by p55PIK-PI3K leads to Imatinib-resistance in patients with gastrointestinal stromal tumors. Oncotarget. 2016;7:1367–79.PubMed
2.
Lasota J, Miettinen M. KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs). Semin Diagn Pathol. 2006;23:91–102.CrossRefPubMed
3.
Li J, Dang Y, Gao J, Li Y, Zou J, Shen L. PI3K/AKT/mTOR pathway is activated after imatinib secondary resistance in gastrointestinal stromal tumors (GISTs). Med Oncol. 2015;32:111.CrossRefPubMed
4.
Evers B, Jastrzebski K, Heijmans JP, Grernrum W, Beijersbergen RL, Bernards R. CRISPR knockout screening outperforms shRNA and CRISPRi in identifying essential genes. Nat Biotechnol. 2016;34:631–3.CrossRefPubMed
5.
Kurata M, Rathe SK, Bailey NJ, Aumann NK, Jones JM, Veldhuijzen GW, Moriarity BS, Largaespada DA. Using genome-wide CRISPR library screening with library resistant DCK to find new sources of Ara-C drug resistance in AML. Sci Rep. 2016;6:36199.CrossRefPubMedPubMedCentral
6.
Al-Achkar W, Wafa A, Moassass F, Othman MA. A novel dic (17,18) (p13.1;q11.2) with loss of TP53 and BCR/ABL rearrangement in an Imatinib resistant chronic myeloid leukemia. Mol Cytogenet. 2012;5:36.CrossRefPubMedPubMedCentral
7.
Shen R, Wang Y, Wang CX, Yin M, Liu HL, Chen JP, Han JQ, Wang WB. MiRNA-155 mediates TAM resistance by modulating SOCS6-STAT3 signalling pathway in breast cancer. Am J Transl Res. 2015;7:2115–26.PubMedPubMedCentral
8.
Bouchard L, Vohl MC, Deshaies Y, Rheaume C, Daris M, Tchernof A. Visceral adipose tissue zinc finger protein 36 mRNA levels are correlated with insulin, insulin resistance index, and adiponectinemia in women. Eur J Endocrinol. 2007;157:451–7.CrossRefPubMed
9.
Liang YN, Tang YL, Ke ZY, Chen YQ, Luo XQ, Zhang H, Huang LB. MiR-124 contributes to glucocorticoid resistance in acute lymphoblastic leukemia by promoting proliferation, inhibiting apoptosis and targeting the glucocorticoid receptor. J Steroid Biochem Mol Biol. 2017;172:62–8.CrossRefPubMed
10.
Zheng Q, Cao J, Hamad N, Kim HJ, Moon JH, Sohn SK, Jung CW, Lipton JH, Kim DD. Single nucleotide polymorphisms in apoptosis pathway are associated with response to imatinib therapy in chronic myeloid leukemia. J Transl Med. 2016;14:82.CrossRefPubMedPubMedCentral
Metadata
Title
Genome-scale CRISPR-Cas9 knockout screening in gastrointestinal stromal tumor with Imatinib resistance
Authors
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
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2018
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-018-0865-2

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