Mateusz Bujko1, Paulina Kober1, Joanna Boresowicz1, Natalia Rusetska1, Natalia Zeber-Lubecka2, Agnieszka Paziewska3, Monika Pekul4, Grzegorz Zielinski5, Andrzej Styk5, Jacek Kunicki6, Jerzy Ostrowski2,7, Janusz A Siedlecki1, Maria Maksymowicz4. 1. Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Institute-Oncology Center, 02-781 Warsaw, Poland. 2. Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Centre for Postgraduate Education, 01-813 Warsaw, Poland. 3. Department of Neuroendocrinology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland. 4. Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Institute-Oncology Center, 02-781 Warsaw, Poland. 5. Department of Neurosurgery, Military Institute of Medicine, 04-141 Warsaw, Poland. 6. Department of Neurosurgery, Maria Sklodowska-Curie Institute-Oncology Center, 02-781 Warsaw, Poland. 7. Department of Genetics, Maria Sklodowska-Curie Institute-Oncology Center, 02-781 Warsaw, Poland.
Abstract
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. 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.
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. 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.
Authors: Adriana Albani; Luis G Pérez-Rivas; Christina Dimopoulou; Stephanie Zopp; Paula Colón-Bolea; Sigrun Roeber; Jürgen Honegger; Jörg Flitsch; Walter Rachinger; Michael Buchfelder; Günter K Stalla; Jochen Herms; Martin Reincke; Marily Theodoropoulou Journal: Clin Endocrinol (Oxf) Date: 2018-06-29 Impact factor: 3.478
Authors: Pietro Locantore; Rosa Maria Paragliola; Gianluca Cera; Roberto Novizio; Ettore Maggio; Vittoria Ramunno; Andrea Corsello; Salvatore Maria Corsello Journal: Int J Mol Sci Date: 2022-06-19 Impact factor: 6.208