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-突变型和野生型促肾上腺皮质激素垂体瘤中微小RNA的差异表达反映了蛋白质泛素化过程的差异。

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

作者信息

Bujko Mateusz, Kober Paulina, Boresowicz Joanna, Rusetska Natalia, Zeber-Lubecka Natalia, Paziewska Agnieszka, Pekul Monika, Zielinski Grzegorz, Styk Andrzej, Kunicki Jacek, Ostrowski Jerzy, Siedlecki Janusz A, Maksymowicz Maria

机构信息

Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Institute-Oncology Center, 02-781 Warsaw, Poland.

Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Centre for Postgraduate Education, 01-813 Warsaw, Poland.

出版信息

J Clin Med. 2021 Jan 20;10(3):375. doi: 10.3390/jcm10030375.

DOI:10.3390/jcm10030375
PMID:33498176
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7863919/
Abstract

BACKGROUND

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 -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 ( = 28) and silent corticotroph tumors ( = 20) were included. mutations were identified with Sanger sequencing. MicroRNA and gene expression was determined with next-generation sequencing.

RESULTS

-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 -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 -mutated and wild-type tumors.

CONCLUSIONS

Differences in microRNA expression in corticotropinomas stratified according to status reflect disturbed ubiquitination processes, but do not correspond to differences in gene expression between these tumors.

摘要

背景

突变是促肾上腺皮质激素垂体瘤中最常见的驱动性改变。它们通过干扰泛素化过程对细胞蛋白质组产生直接影响，并且还影响基因表达。本研究的目的是比较携带突变和野生型肿瘤中的微小RNA谱，并通过综合微小RNA和mRNA分析确定差异微小RNA表达的可能作用。

方法

纳入库欣病患者（n = 28）和无功能促肾上腺皮质激素瘤患者（n = 20）。通过桑格测序鉴定突变。用下一代测序确定微小RNA和基因表达。

结果

携带突变的库欣病患者显示出比野生型患者更高的临床缓解率和肿瘤体积减小的趋势。比较携带突变和野生型肿瘤的微小RNA谱发现68个差异表达的微小RNA。通过计算机预测和微小RNA/mRNA相关性分析确定它们的靶基因。对推定靶标的基因集富集分析表明，最显著富集的基因参与蛋白质泛素化相关过程。只有少数微小RNA影响携带突变和野生型肿瘤之间差异表达基因的表达。

结论

根据突变状态分层的促肾上腺皮质激素瘤中微小RNA表达的差异反映了泛素化过程的紊乱，但与这些肿瘤之间的基因表达差异不对应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da66/7863919/88adfb6fac07/jcm-10-00375-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da66/7863919/d3cc552467e1/jcm-10-00375-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da66/7863919/65dca6630cf9/jcm-10-00375-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da66/7863919/88adfb6fac07/jcm-10-00375-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da66/7863919/d3cc552467e1/jcm-10-00375-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da66/7863919/65dca6630cf9/jcm-10-00375-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da66/7863919/88adfb6fac07/jcm-10-00375-g003.jpg

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