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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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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

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

Project description: Not available

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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

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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.

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

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

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Microarray analysis of an RXR agonist HX630 regulated gene expression in murine pituitary corticotroph tumor cells (AtT20 cell)

Project description:To gain insight into the functional mechanisms of an RXR agonist HX630 in murine pituitary corticotroph tumor cells (AtT20 cell), especially concerning cell proliferation and apoptosis, we conducted whole genome microarray analysis to identify gene expression patterns, networks, and pathways in AtT20 cells treated with HX630 at 10 μM for 48 hr. 2,173 up-regulated and 3,169 down-regulated genes were identified that demonstrated fold-changes of at least 1.5 and a P-value <0.01 in AtT20 cells with HX630 at 10 uM compared with control. Both the up- and down-regulated differentially expressed genes were submitted to IPA, which groups significant genes according to biological processes in which they function, and identifies various functions, networks, and pathways. These analyses showed that the categories of the biological functions and diseases significantly regulated by HX630 were associated with cell death, growth and cancer. Furthermore, it was identified that a gene network associated with caspase 3 was significantly induced by HX630.These data indicated that HX630 induced cell death and suppressed cell growth in AtT20 cells, consistent with the results of in vitro studies.

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miRNA landscape of corticotroph pituitary neuroendocrine tumor from bilateral petrosal sinus sampling

Project description:miRNA landscape of corticotroph pituitary neuroendocrine tumor from bilateral petrosal sinus sampling

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Microarray analysis of an RXR agonist HX630 regulated gene expression in murine pituitary corticotroph tumor cells (AtT20 cell)

Project description:To gain insight into the functional mechanisms of an RXR agonist HX630 in murine pituitary corticotroph tumor cells (AtT20 cell), especially concerning cell proliferation and apoptosis, we conducted whole genome microarray analysis to identify gene expression patterns, networks, and pathways in AtT20 cells treated with HX630 at 10 M-NM-<M for 48 hr. 2,173 up-regulated and 3,169 down-regulated genes were identified that demonstrated fold-changes of at least 1.5 and a P-value <0.01 in AtT20 cells with HX630 at 10 uM compared with control. Both the up- and down-regulated differentially expressed genes were submitted to IPA, which groups significant genes according to biological processes in which they function, and identifies various functions, networks, and pathways. These analyses showed that the categories of the biological functions and diseases significantly regulated by HX630 were associated with cell death, growth and cancer. Furthermore, it was identified that a gene network associated with caspase 3 was significantly induced by HX630.These data indicated that HX630 induced cell death and suppressed cell growth in AtT20 cells, consistent with the results of in vitro studies. AtT20 cells grown to 50 % confluence in regular medium in 12-multiwell plates were incubated either without or with HX630 at 10 M-NM-<M in DMEM supplemented with 1 % stripped FBS media for 48 hr. The cells were then lysed and their total RNAs were isolated for microarray analysis.

2013-01-27 | E-GEOD-43783 | biostudies-arrayexpress

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