The cancer-associated microprotein CASIMO1 controls cell proliferation and interacts with squalene epoxidase modulating lipid droplet formation

Oncogene
Maria Polycarpou-SchwarzSven Diederichs

Abstract

Breast cancer is a leading cause of cancer-related death in women. Small open reading frame (sORF)-encoded proteins or microproteins constitute a new class of molecules often transcribed from presumed long non-coding RNA transcripts (lncRNAs). The translation of some of these sORFs has been confirmed, but their cellular function and importance remains largely unknown. Here, we report the identification and characterization of a novel microprotein of 10 kDa, which we named Cancer-Associated Small Integral Membrane Open reading frame 1 (CASIMO1). CASIMO1 RNA is overexpressed predominantly in hormone receptor-positive breast tumors. Its knockdown leads to decreased proliferation in multiple breast cancer cell lines. Its loss disturbs the organization of the actin cytoskeleton, leads to inhibition of cell motility, and causes a G0/G1 cell cycle arrest. The proliferation phenotype upon overexpression is observed only with CASIMO1 protein expression, but not with a non-translatable mutant attributing the effects to the sORF-derived protein rather than a lncRNA function. CASIMO1 microprotein interacts with squalene epoxidase (SQLE), a key enzyme in cholesterol synthesis and a known oncogene in breast cancer. Overexpression of CASIMO1 ...Continue Reading

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Datasets Mentioned

BETA
KX065456

Methods Mentioned

BETA
reverse
transfection
FACS
fluorescence-activated cell sorting
immunoprecipitation
co-immunoprecipitation
flow cytometry
fluorescence activated cell sorting

Software Mentioned

ImageJ
Expasy
FlowJo
TANRIC
LabImage
Fiji
Gene Set Enrichment Analysis ( GSEA )
xcellence rt

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