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Differential microRNA Expression in USP8-Mutated and Wild-Type Corticotroph Pituitary Tumors Reflect the Difference in Protein Ubiquitination Processes

ABSTRACT: Differential microRNA Expression in USP8-Mutated and Wild-Type Corticotroph Pituitary Tumors Reflect the Difference in Protein Ubiquitination Processes

PROVIDER: PRJNA699914 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13644417.fastq.gz	Fastqsanger.gz
	SRR13644418.fastq.gz	Fastqsanger.gz
	SRR13644419.fastq.gz	Fastqsanger.gz
	SRR13644420.fastq.gz	Fastqsanger.gz
	SRR13644421.fastq.gz	Fastqsanger.gz

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Similar Datasets

Differential microRNA Expression in USP8-Mutated and Wild-Type Corticotroph Pituitary Tumors Reflect the Difference in Protein Ubiquitination Processes

Project description:Background: USP8 mutations are the most common driver changes in corticotroph pituitary tumors. They have direct effect on cells’ proteome through disturbance of ubiquitination process and also influence gene expression. The aim of this study was to compare microRNA profiles in USP8- mutated and wild-type tumors and determine the probable role of differential microRNA expression by integrative microRNA and mRNA analysis. Methods: Patients with Cushing’s disease (n = 28) and silent corticotroph tumors (n = 20) were included. USP8 mutations were identified with Sanger sequencing. MicroRNA and gene expression was determined with next-generation sequencing. Results: USP8-mutated patients with Cushing’s disease showed higher rate of clinical remission and trend towards lower tumor volume than wild-type patients. Comparison of microRNA profiles of USP8-mutated and wild-type tumors revealed 68 differentially expressed microRNAs. Their target genes were determined by in silico prediction and microRNA/mRNA correlation analysis. GeneSet Enrichment analysis of putative targets showed that the most significantly overrepresented genes are involved in protein ubiquitination-related processes. Only few microRNAs influence the expression of genes differentially expressed between USP8-mutated and wild-type tumors. Conclusions: Differences in microRNA expression in corticotropinomas stratified according to USP8 status reflect disturbed ubiquitination processes, but do not correspond to differences in gene expression between these tumors.

2021-02-06 | GSE166279 | GEO

USP8 mutations determine genes’ expression profile of pituitary corticotroph adenomas, regardless of tumor functional status.

Project description:The aim of the study was to compare genes’ expression profiles of functioning and silent corticotroph adenomas to investigate possible biological mechanism of different hormone secretion . Since USP8 is the best know driver gene mutated in large proportion of ACTH-omas we intended to verify whether the mutation occurs in SCAs and how it affects transcriptomic profile.

2019-06-20 | GSE132982 | GEO

Differential microRNA Expression in <i>USP8</i>-Mutated and Wild-Type Corticotroph Pituitary Tumors Reflect the Difference in Protein Ubiquitination Processes.

Project description:BackgroundUSP8 mutations are the most common driver changes in corticotroph pituitary tumors. They have direct effect on cells' proteome through disturbance of ubiquitination process and also influence gene expression. The aim of this study was to compare microRNA profiles in USP8-mutated and wild-type tumors and determine the probable role of differential microRNA expression by integrative microRNA and mRNA analysis.MethodsPatients with Cushing's disease (n = 28) and silent corticotroph tumors (n = 20) were included. USP8 mutations were identified with Sanger sequencing. MicroRNA and gene expression was determined with next-generation sequencing.ResultsUSP8-mutated patients with Cushing's disease showed higher rate of clinical remission and trend towards lower tumor volume than wild-type patients. Comparison of microRNA profiles of USP8-mutated and wild-type tumors revealed 68 differentially expressed microRNAs. Their target genes were determined by in silico prediction and microRNA/mRNA correlation analysis. GeneSet Enrichment analysis of putative targets showed that the most significantly overrepresented genes are involved in protein ubiquitination-related processes. Only few microRNAs influence the expression of genes differentially expressed between USP8-mutated and wild-type tumors.ConclusionsDifferences in microRNA expression in corticotropinomas stratified according to USP8 status reflect disturbed ubiquitination processes, but do not correspond to differences in gene expression between these tumors.

| S-EPMC7863919 | biostudies-literature

USP8 mutations determine genes’ expression profile of pituitary corticotroph adenomas, regardless of tumor functional status.

Project description:USP8 mutations determine genes’ expression profile of pituitary corticotroph adenomas, regardless of tumor functional status.

| PRJNA549652 | ENA

SST5 expression and USP8 mutation in functioning and silent corticotroph pituitary tumors.

Project description:OBJECTIVE:Somatostatin receptor type 5 (SST5) is inconsistently expressed by corticotroph tumors, with higher expression found in corticotropinomas having ubiquitin-specific protease 8 (USP8) mutations. Aims were to study the correlation between characteristics of corticotropinomas and SST5 expression/USP8 mutation status and to describe the response to pasireotide in 5 patients. DESIGN:Retrospective cohort study. METHODS:Clinico-biochemical, radiological and pathological data of 62 patients, operated for a functioning or silent corticotropinoma between 2013 and 2017, were collected. SST5 expression was measured by immunohistochemistry (clone UMB-4, Abcam, IRS>1 being considered positive) and Sanger sequencing was performed on 50 tumors to screen for USP8 mutations. RESULTS:SST5 expression was positive in 26/62 pituitary tumors. A moderate or strong IRS was found in 15/58 corticotropinomas and in 13/35 functioning corticotropinomas. Among functioning tumors, those expressing SST5 were more frequent in women (22/24 vs 9/15, P=0.04) and had a lower grade (P=0.04) compared to others. USP8 mutations were identified in 13/50 pituitary tumors and were more frequent in functioning compared to silent tumors (11/30 vs 2/20, P=0.05). SST5 expression was more frequent in USP8mut vs USP8wt tumors (10/11 vs 7/19, P=0.007). Among treated patients, normal urinary free cortisol levels were obtained in 3 patients (IRS 0, 2, 6) while a 4-fold decrease was observed in one patient (IRS 4). CONCLUSION:SST5 expression appears to be associated with functioning, USP8mut and lower grade corticotropinomas. A correlation between SST5 expression or USP8mut and response to pasireotide remains to be confirmed.

| S-EPMC7077525 | biostudies-literature

Transcriptome profiling of wild-type (WT) and USP8 knockout (KO) CT26 cell lines

Project description:USP8 is one of DUBs and is frequently overexpressed or gain-of-function mutated in multiple types of human cancer. Importantly, USP8 has been identified as an immunomodulatory DUB as T cell-specific Usp8 deficiency disrupts regulatory T cell functions, leading to recruiting abundant CD8+ T cells in colons and resulting in the inflammatory bowel disease in mice. However, whether targeting USP8 can enhance anti-tumor immunity has not been reported. To further explore the physiological function of USP8, we performed the transcriptomic analysis to comprehensively understand which signaling pathways are mainly regulated by USP8 in cancer cells. Usp8 WT and KO CT26 cells were harvested for RNA-sequencing (RNA-seq).

2022-02-14 | GSE164558 | GEO

Trancriptome analysis of tumor tissue to search for the associations between USP8 mutation status, molecular markers of pituitary adenomas, and clinical, and diagnostic parametres of Cushing disease

Project description:In this work we employed the comprehensive evaluation of clinical data of the cohort of CD patients along with the sequencing of 14 exon of USP8 to estimate the prevalence of USP8 mutations in our cohort and transcriptome analysis of tumor tissue to search for the associations between USP8 mutation status, molecular markers of pituitary adenomas, and clinical and diagnostic parameters of Cushing’s syndrome including hormonal secretion, tumor size, aggressiveness, and SSRT2/SSRT5 expression.

2024-04-11 | GSE263206 | GEO

Murine corticotroph pituitary AtT-20 cells: Crh treatment time course

Project description:As the Crh-system and the HPA-axis are known to be crucially involved in the onset, development and maintainance of psychiatric disorders like anxiety and depression and regulate the behavioural and endocrine stress responses the further analysis of Crhr1-dependent signaling cascades is essential to understand the molecular mechanisms behind these psychiatric diseases. In this project, new candidate genes involved in Crhr1-dependent signaling cascades were dissected in the cell line model of AtT-20 cells by transcriptional profiling of mouse pituitary corticotroph cells comparing control untreated AtT-20 cells with AtT-20 cells treated with 100 nM Crh at 1, 3, 6, 12 and 24 hours. Keywords: time course, treatment response

2009-01-31 | GSE13156 | GEO

Murine corticotroph pituitary AtT-20 cells: Crh treatment time course

2010-05-06 | E-GEOD-13156 | biostudies-arrayexpress

Knockdown of transcription factor Creb3l1 in anterior pituitary mouse corticotroph cell line AtT20

Project description:Transcription factor Creb3l1 is a non-classical ER stress molecule that is emerging as an important component for cellular homeostasis, particularly within cell-types with high peptide secretory capabilities. We have previously shown that Creb3l1 serves an important role in body fluid homeostasis through its transcriptional control of the gene coding for antidiuretic hormone arginine vasopressin in the neuropeptide rich magnocellular neurons of the supraoptic nucleus. To identify other genes regulated by transcription factor Creb3l1 in secretory cells, we performed RNA-sequencing of Creb3l1 knockdown anterior pituitary mouse corticotroph cell line AtT20.

2020-04-03 | GSE147978 | GEO

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