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Title: Elevated SGPL1 expression increases metabolic rate and reduces survival in adrenocortical carcinoma patients

ABSTRACT: Title: Elevated SGPL1 expression increases metabolic rate and reduces survival in adrenocortical carcinoma patients

PROVIDER: PRJNA786217 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17130504_1.fastq.gz	Fastqsanger.gz
	SRR17130504_2.fastq.gz	Fastqsanger.gz
	SRR17130505_1.fastq.gz	Fastqsanger.gz
	SRR17130505_2.fastq.gz	Fastqsanger.gz
	SRR17130506_1.fastq.gz	Fastqsanger.gz

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Title: Elevated SGPL1 expression increases metabolic rate and reduces survival in adrenocortical carcinoma patients

Project description:Sphingosine-1-phosphate lyase (SGPL1) catalyses the final step in sphingolipid metabolism (Figure 1), irreversibly degrading the lipid signalling molecule sphingosine-1-phosphate (S1P). Loss-of-function mutations in SGPL1 cause a spectrum of disorders, including primary adrenal insufficiency. Given loss of SGPL1 causes reduced steroidogenesis, while increased steroidogenesis is a hallmark of aggressive adrenocortical carcinomas (ACCs), we hypothesise increased SGPL1 expression might regulate ACCs. We identified a potential novel biomarker in ACCs, whereby increased SGPL1 expression correlates with reduced patient survival. We also saw similar correlation with other sphingolipid enzymes which diminish the ceramide pool, while those that replenish it confer a beneficial patient outcome. Increased SGPL1 expression in a cell model increased their resting proliferation and migration, although no effect on apoptosis was seen. There was a global decrease in the sphingolipid pool, possibly indicating increased flux through this pathway. RNAseq analysis identified an increase in expression of oxidative phosphorylation genes, and this correlated with an increase in basal and maximal glycolysis and oxidative phosphorylation. Finally, we showed that the increase in proliferation in the OE cells is dependent on the presence of metabolic substrates which may be used for anabolism and/or the production of ATP.

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Metastatic adrenocortical carcinoma displays higher mutation rate and tumor heterogeneity than primary tumors

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Project description:Adrenocortical tumors are common; their prevalence may reach up to 5-7% in pathological series. Most of them are benign and hormonally inactive, however, rare hormone-secreting (aldosterone and cortisol) and malignant forms are associated with significant morbidity and mortality. The prognosis of adrenocortical cancer (ACC) is poor with an overall five-year survival below 30 %. In this study, CGH analysis was performed on 4 ACC (adrenocortical carcinoma), 4 IA (hormonally inactive adrenocortical adenoma) and 3 CPA (cortisol producing adrenocortical adenoma) samples. Tissue digestion, labeling, hybridization and data analysis of genomic DNA were performed according to the Agilent Technologies (Santa Clara, CA) protocol version 2.0 for 105 K arrays. As expected, many of the observed aberrations were generally consistent with those of other preciously published data and will provide the basis for determination how genomic diversity impacts biological function and human diseases, such as cancer.

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Analysis of circulating microRNAs in adrenocortical tumours

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