Pheno-RNA, a method to associate genes with a specific phenotype, identifies genes linked to cellular transformation.
Animals
Biological Variation, Population
/ genetics
Cell Line, Transformed
Cell Line, Tumor
Cell Transformation, Neoplastic
/ genetics
Gene Expression Profiling
/ methods
Gene Expression Regulation, Neoplastic
/ genetics
Genetic Association Studies
/ methods
Humans
Phenotype
RNA
/ genetics
Transformation, Genetic
/ genetics
cancer
cellular transformation
mRNA profiling
phenotypic analysis
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
17 11 2020
17 11 2020
Historique:
pubmed:
5
11
2020
medline:
15
1
2021
entrez:
4
11
2020
Statut:
ppublish
Résumé
Cellular transformation is associated with dramatic changes in gene expression, but it is difficult to determine which regulated genes are oncogenically relevant. Here we describe Pheno-RNA, a general approach to identifying candidate genes associated with a specific phenotype. Specifically, we generate a "phenotypic series" by treating a nontransformed breast cell line with a wide variety of molecules that induce cellular transformation to various extents. By performing transcriptional profiling across this phenotypic series, the expression profile of every gene can be correlated with the strength of the transformed phenotype. We identify ∼200 genes whose expression profiles are very highly correlated with the transformation phenotype, strongly suggesting their importance in transformation. Within biological categories linked to cancer, some genes show high correlations with the transformed phenotype, but others do not. Many genes whose expression profiles are highly correlated with transformation have never been associated with cancer, suggesting the involvement of heretofore unknown genes in cancer.
Identifiants
pubmed: 33144504
pii: 2014165117
doi: 10.1073/pnas.2014165117
pmc: PMC7682411
doi:
Substances chimiques
RNA
63231-63-0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
28925-28929Subventions
Organisme : NCI NIH HHS
ID : R01 CA107486
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no competing interests.
Références
PLoS One. 2014 Mar 17;9(3):e92023
pubmed: 24637666
Cell. 1979 Feb;16(2):443-52
pubmed: 378392
Proc Natl Acad Sci U S A. 2019 May 7;116(19):9453-9462
pubmed: 30910960
Nat Rev Genet. 2018 May;19(5):299-310
pubmed: 29479082
Curr Protoc Mol Biol. 2015 Apr 01;110:4.23.1-4.23.17
pubmed: 25827089
PLoS Genet. 2015 Jun 03;11(6):e1005195
pubmed: 26039065
Nat Commun. 2018 May 25;9(1):2068
pubmed: 29802342
J Bacteriol. 1967 May;93(5):1662-70
pubmed: 5337848
Mol Cell. 2010 Aug 27;39(4):493-506
pubmed: 20797623
Nat Genet. 1999 Jan;21(1 Suppl):20-4
pubmed: 9915496
Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16693-8
pubmed: 21930916
Cancer Cell. 2010 Apr 13;17(4):348-61
pubmed: 20385360
Sci Rep. 2019 Dec 10;9(1):18696
pubmed: 31822756
Cell. 2009 Nov 13;139(4):693-706
pubmed: 19878981
Nature. 1980 Oct 30;287(5785):795-801
pubmed: 6776413
Nucleic Acids Res. 2018 Nov 2;46(19):e116
pubmed: 30011038
Cell Syst. 2017 Aug 23;5(2):140-148.e2
pubmed: 28822752
Proc Natl Acad Sci U S A. 2015 May 5;112(18):5708-13
pubmed: 25902495
Nat Rev Mol Cell Biol. 2014 Sep;15(9):591-600
pubmed: 25145850
Science. 1995 Oct 20;270(5235):467-70
pubmed: 7569999
Cancer Res. 1990 Sep 15;50(18):6075-86
pubmed: 1975513
Sci Rep. 2018 Jan 19;8(1):1237
pubmed: 29352257
Nat Rev Genet. 2009 Jan;10(1):57-63
pubmed: 19015660