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

TitleGenome-wide CRISPR-based gene knockout screens reveal cellular factors and pathways essential for nasopharyngeal carcinoma
Authors
Keywordscancer biology
CRISPR/Cas
glucose
purine
NF-κB
Issue Date2019
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal of Biological Chemistry, 2019, v. 294 n. 25, p. 9734-9745 How to Cite?
AbstractEarly 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.
Persistent Identifierhttp://hdl.handle.net/10722/293222
ISSN
2019 Impact Factor: 4.238
2015 SCImago Journal Rankings: 3.151
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, C-
dc.contributor.authorJiang, S-
dc.contributor.authorKe, L-
dc.contributor.authorZhang, L-
dc.contributor.authorLi, D-
dc.contributor.authorLiang, J-
dc.contributor.authorNarita, Y-
dc.contributor.authorHou, I-
dc.contributor.authorChen, CH-
dc.contributor.authorWang, L-
dc.contributor.authorZhong, Q-
dc.contributor.authorLing, Y-
dc.contributor.authorLv, XING-
dc.contributor.authorXiang, Y-
dc.contributor.authorGuo, X-
dc.contributor.authorTeng, M-
dc.contributor.authorTsao, SW-
dc.contributor.authorGewurz, BE-
dc.contributor.authorZeng, MS-
dc.contributor.authorZhao, B-
dc.date.accessioned2020-11-23T08:13:36Z-
dc.date.available2020-11-23T08:13:36Z-
dc.date.issued2019-
dc.identifier.citationJournal of Biological Chemistry, 2019, v. 294 n. 25, p. 9734-9745-
dc.identifier.issn0021-9258-
dc.identifier.urihttp://hdl.handle.net/10722/293222-
dc.description.abstractEarly 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.-
dc.languageeng-
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/-
dc.relation.ispartofJournal of Biological Chemistry-
dc.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.-
dc.rightsThis research was originally published in the [Journal Name]. Author(s). Title. Journal Name. Year; Vol:pp-pp. © the American Society for Biochemistry and Molecular Biology or © the Author(s).-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectcancer biology-
dc.subjectCRISPR/Cas-
dc.subjectglucose-
dc.subjectpurine-
dc.subjectNF-κB-
dc.titleGenome-wide CRISPR-based gene knockout screens reveal cellular factors and pathways essential for nasopharyngeal carcinoma-
dc.typeArticle-
dc.identifier.emailTsao, SW: gswtsao@hku.hk-
dc.identifier.authorityTsao, SW=rp00399-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1074/jbc.RA119.008793-
dc.identifier.pmid31073033-
dc.identifier.pmcidPMC6597810-
dc.identifier.scopuseid_2-s2.0-85068455591-
dc.identifier.hkuros319481-
dc.identifier.volume294-
dc.identifier.issue25-
dc.identifier.spage9734-
dc.identifier.epage9745-
dc.identifier.isiWOS:000473277900009-
dc.publisher.placeUnited States-
dc.identifier.issnl0021-9258-

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