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

Mol Cancer. 2018 Aug 13;17(1):121. doi: 10.1186/s12943-018-0865-2.

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.

Keywords: Gastrointestinal stromal tumor; Genome-scale CRISPR-Cas9 knockout screening; Imatinib resistance.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CRISPR-Cas Systems
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm*
  • Gastrointestinal Neoplasms / genetics*
  • Gastrointestinal Stromal Tumors / genetics*
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks*
  • Humans
  • Imatinib Mesylate
  • Signal Transduction

Substances

  • Imatinib Mesylate