Genomics

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Cholesterol homeostasis modulates platinum sensitivity in human ovarian cancer


ABSTRACT: Here we show that platinum-resistant ovarian cancer cells also show reduced cholesterol biosynthesis, and mostly rely on uptake of exogenous cholesterol for their needs. Expression of FDPS and OSC, enzymes involved in cholesterol synthesis, are decreased both in drug-resistant cells and upon TRAP1 silencing, whereas the expression of LDL receptor, the main mediator of extracellular cholesterol uptake, is increased. Strikingly, treatment with different statins to inhibit cholesterol synthesis reduces cisplatin-induced apoptosis, whereas silencing of LIPG, an enzyme involved in lipid metabolism, increases sensitivity to the drug. Overall design: Evaluation of differentially expressed transcripts in PEA1 ovarian cancer cells following transfection with TRAP1-directed siRNA or control siRNA

INSTRUMENT(S): Illumina HumanHT-12 V4.0 expression beadchip

ORGANISM(S): Homo sapiens  

SUBMITTER: Danilo Swann Matassa  

PROVIDER: GSE144248 | GEO | 2020-05-21

REPOSITORIES: GEO

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Publications


Despite initial chemotherapy response, ovarian cancer is the deadliest gynecologic cancer, due to frequent relapse and onset of drug resistance. To date, there is no affordable diagnostic/prognostic biomarker for early detection of the disease. However, it has been recently shown that high grade serous ovarian cancers show peculiar oxidative metabolism, which is in turn responsible for inflammatory response and drug resistance. The molecular chaperone TRAP1 plays pivotal roles in such metabolic  ...[more]

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