دورية أكاديمية
Deregulation of miRNAs-cMYC circuits is a key event in refractory celiac disease type-2 lymphomagenesis.
| العنوان: | Deregulation of miRNAs-cMYC circuits is a key event in refractory celiac disease type-2 lymphomagenesis. |
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| المؤلفون: | Vaira V; Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Gaudioso G; Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy., Laginestra MA; Hematopathology Unit, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy., Terrasi A; Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Agostinelli C; Hematopathology Unit, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy., Bosari S; Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy., Di Sabatino A; Department of Internal Medicine San Matteo Hospital, University of Pavia, Pavia, Italy., Vanoli A; Department of Molecular Medicine San Matteo Hospital, University of Pavia, Pavia, Italy., Paulli M; Department of Molecular Medicine San Matteo Hospital, University of Pavia, Pavia, Italy., Ferrero S; Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy., Roncoroni L; Center for the Prevention and Diagnosis of Celiac Disease, Division of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy., Lombardo V; Center for the Prevention and Diagnosis of Celiac Disease, Division of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Perera LP; Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD 20892, U.S.A., Fabris S; Division of Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Vecchi M; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.; Center for the Prevention and Diagnosis of Celiac Disease, Division of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Pileri S; Division of Haematopathology, European Institute of Oncology, Milan, Italy., Elli L; Center for the Prevention and Diagnosis of Celiac Disease, Division of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. |
| المصدر: | Clinical science (London, England : 1979) [Clin Sci (Lond)] 2020 May 29; Vol. 134 (10), pp. 1151-1166. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Portland Press on behalf of the Medical Research Society and the Biochemical Society Country of Publication: England NLM ID: 7905731 Publication Model: Print Cited Medium: Internet ISSN: 1470-8736 (Electronic) Linking ISSN: 01435221 NLM ISO Abbreviation: Clin Sci (Lond) Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: London : Portland Press on behalf of the Medical Research Society and the Biochemical Society Original Publication: London, Medical Research Society. |
| مواضيع طبية MeSH: | Gene Expression Regulation, Neoplastic*, Carcinogenesis/*genetics , Celiac Disease/*genetics , Lymphoma/*genetics , MicroRNAs/*genetics , Proto-Oncogene Proteins c-myc/*metabolism, Algorithms ; Animals ; Biomarkers, Tumor/metabolism ; Female ; Intestines/pathology ; Lymphoma/pathology ; Male ; Mice, Transgenic ; MicroRNAs/metabolism ; Models, Biological ; Prognosis ; Proto-Oncogene Proteins c-mdm2/metabolism ; Smad3 Protein/metabolism ; Up-Regulation/genetics |
| مستخلص: | A percentage of celiac disease (CD) patients develop refractory type-2 disease (RCD2), a condition associated with increased risk of enteropathy-associated T-cell-lymphoma (EATL) and without therapeutic option. Therefore, we profiled the miRNome in series of peripheral T-cell lymphomas (PTCLs), CD, RCD1 or 2 and in the murine interleukin-15 (IL15)-transgenic (TG) model of RCD. The transcriptome was analyzed in 18 intestinal T-cell lymphomas (ITLs). Bioinformatics pipelines provided significant microRNA (miRNA) lists and predicted targets that were confirmed in a second set of patients. Our data show that ITLs have a unique miRNA profile with respect to other PTCLs. The c-MYC regulated miR-17/92 cluster distinguishes monomorphic epitheliotropic ITL (MEITL) from EATL and prognosticates EATL outcome. These miRNAs are decreased in IL15-TG mice upon Janus kinase (JAK) inhibition. The random forest algorithm identified a signature of 38 classifier miRNAs, among which, the miR-200 and miR-192/215 families were progressively lost in RCD2 and ITL-CD, whereas miR-17/92 and C19MC miRNAs were up-regulated. Accordingly, SMAD3, MDM2, c-Myc and activated-STAT3 were increased in RCD2 and EATL tissues while JAK inhibition in IL15-TG mice restored their levels to baseline. Our data suggest that miRNAs circuit supports activation of STAT3 and c-Myc oncogenic signaling in RCD2, thus contributing to lymphomagenesis. This novel understanding might pave the way to personalized medicine approaches for RCD and EATL. (© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.) |
| فهرسة مساهمة: | Keywords: EATL; Myc; RCD type 2; celiac disease; miR-17/92 |
| المشرفين على المادة: | 0 (Biomarkers, Tumor) 0 (MicroRNAs) 0 (Proto-Oncogene Proteins c-myc) 0 (Smad3 Protein) EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2) |
| تواريخ الأحداث: | Date Created: 20200519 Date Completed: 20201007 Latest Revision: 20201007 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1042/CS20200032 |
| PMID: | 32420596 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1470-8736 |
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| DOI: | 10.1042/CS20200032 |