Genome-wide CRISPR screen reveals PSMA6 to be an essential gene in pancreatic cancer cells. BMC Cancer 2019 Mar 21;19(1):253
Date
03/23/2019Pubmed ID
30898113Pubmed Central ID
PMC6429770DOI
10.1186/s12885-019-5455-1Scopus ID
2-s2.0-85063331223 (requires institutional sign-in at Scopus site) 20 CitationsAbstract
BACKGROUND: Despite its relatively low incidence, pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer deaths because of the aggressive growth/metastasis of the tumor, the lack of early symptoms, and the poor treatment options. Basic research to identify potential therapeutic targets for PDAC is greatly needed.
METHODS: We used a negative-selection genome-wide CRISPR screen to identify essential genes in the PANC-1 human pancreatic carcinoma cell line. We validated the top hits with follow-up siRNA screens, using the HPNE, HPAF-II, AsPC-1, and Mia PaCa-2 cell lines.
RESULTS: The PSMA6 gene was an identified candidate hit after the CRISPR screen, siRNA validation screen, and siRNA deconvolution screen. Spheroid formation assays and flow cytometry analysis showed that PSMA6 is critical for survival in many pancreatic ductal carcinoma cell models. Lastly, as PSMA6 protein is a proteosomal subunit of the 20S core complex, we showed that bortezomib, a proteasome inhibitor, was especially toxic in PANC-1 cells.
CONCLUSIONS: Further study of PSMA6 and the proteasome subunit that it encodes, along with other hits identified in our CRISPR screens, may provide valuable insights into potential therapeutic targets for PDAC.
Author List
Bakke J, Wright WC, Zamora AE, Oladimeji P, Crawford JC, Brewer CT, Autry RJ, Evans WE, Thomas PG, Chen TAuthor
Anthony E. Zamora PhD Assistant Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
BortezomibCarcinoma, Pancreatic Ductal
Cell Line, Tumor
Cell Proliferation
Cell Survival
Clustered Regularly Interspaced Short Palindromic Repeats
Genome, Human
Genomics
Humans
Oncogenes
Pancreas
Pancreatic Neoplasms
Proteasome Endopeptidase Complex
Proteasome Inhibitors
RNA, Small Interfering
Spheroids, Cellular
