Genome-wide CRISPR-based gene knockout screens reveal cellular factors and pathways essential for nasopharyngeal carcinoma

J Biol Chem. 2019 Jun 21;294(25):9734-9745. doi: 10.1074/jbc.RA119.008793. Epub 2019 May 9.


Early diagnosis of nasopharyngeal carcinoma (NPC) is difficult because of a lack of specific symptoms. Many patients have advanced disease at diagnosis, and these patients respond poorly to treatment. New treatments are therefore needed to improve the outcome of NPC. To better understand the molecular pathogenesis of NPC, here we used an NPC cell line in a genome-wide CRISPR-based knockout screen to identify the cellular factors and pathways essential for NPC (i.e. dependence factors). This screen identified the Moz, Ybf2/Sas3, Sas2, Tip60 histone acetyl transferase complex, NF-κB signaling, purine synthesis, and linear ubiquitination pathways; and MDM2 proto-oncogene as NPC dependence factors/pathways. Using gene knock out, complementary DNA rescue, and inhibitor assays, we found that perturbation of these pathways greatly reduces the growth of NPC cell lines but does not affect growth of SV40-immortalized normal nasopharyngeal epithelial cells. These results suggest that targeting these pathways/proteins may hold promise for achieving better treatment of patients with NPC.

Keywords: CRISPR screen; CRISPR/Cas; MYST family proteins; NF-κB; cancer biology; essential genes; glucose; nasopharyngeal carcinoma; purine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / genetics*
  • CRISPR-Cas Systems*
  • Cell Proliferation*
  • Gene Knockout Techniques / methods*
  • Genome, Human*
  • Humans
  • Nasopharyngeal Carcinoma / genetics*
  • Nasopharyngeal Carcinoma / pathology
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / pathology
  • Proto-Oncogene Mas
  • Signal Transduction
  • Tumor Cells, Cultured


  • Biomarkers, Tumor
  • MAS1 protein, human
  • Proto-Oncogene Mas