Squalene epoxidase is a bona fide oncogene by amplification with clinical relevance in breast cancer

Scientific Reports
David N BrownGabriele Zoppoli

Abstract

SQLE encodes squalene epoxidase, a key enzyme in cholesterol synthesis. SQLE has sporadically been reported among copy-number driven transcripts in multi-omics cancer projects. Yet, its functional relevance has never been subjected to systematic analyses. Here, we assessed the correlation of SQLE copy number (CN) and gene expression (GE) across multiple cancer types, focusing on the clinico-pathological associations in breast cancer (BC). We then investigated whether any biological effect of SQLE inhibition could be observed in BC cell line models. Breast, ovarian, and colorectal cancers showed the highest CN driven GE among 8,783 cases from 22 cancer types, with BC presenting the strongest one. SQLE overexpression was more prevalent in aggressive BC, and was an independent prognostic factor of unfavorable outcome. Through SQLE pharmacological inhibition and silencing in a panel of BC cell lines portraying the diversity of SQLE CN and GE, we demonstrated that SQLE inhibition resulted in a copy-dosage correlated decrease in cell viability, and in a noticeable increase in replication time, only in lines with detectable SQLE transcript. Altogether, our results pinpoint SQLE as a bona fide metabolic oncogene by amplification, and a...Continue Reading

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Datasets Mentioned

BETA
GSE71395

Methods Mentioned

BETA
PCR
Feature Extraction

Software Mentioned

ABSOLUTE
R
METABRIC
Feature Extraction
survcomp
SQLE
MASS
FactoMineR
limma BioConductor
GraphPad PRISM

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