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MiR-10a and HOXB4 are overexpressed in atypical myeloproliferative neoplasms

التفاصيل البيبلوغرافية
العنوان: MiR-10a and HOXB4 are overexpressed in atypical myeloproliferative neoplasms
المؤلفون: Arnaud Villacreces, Franck Salin, Vincent Praloran, Philippe Brunet de la Grange, Eric Lippert, Francois-Xavier Mahon, Damien Luque Paz, Junji Koya, Bruno Cardinaud, Mineo Kurokawa, Olivier Mansier, Jean-Max Pasquet, Audrey Bidet, Pierre-Yves Dumas, Valérie Prouzet-Mauléon
المساهمون: CHU Bordeaux [Bordeaux], Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'hématologie, Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), The University of Tokyo (UTokyo), Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement Français du Sang, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Biodiversité, Gènes & Communautés (BioGeCo), Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB), UNICANCER, Institut National Polytechnique, Service d'hématologie biologique, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), ProdInra, Migration
المصدر: BMC Cancer, Vol 18, Iss 1, Pp 1-11 (2018)
BMC Cancer 1 (18), 1-11. (2018)
BMC Cancer
BMC Cancer, BioMed Central, 2018, 18 (1), pp.1-11. ⟨10.1186/s12885-018-4993-2⟩
بيانات النشر: BMC, 2018.
سنة النشر: 2018
مصطلحات موضوعية: 0301 basic medicine, Cancer Research, [SDV]Life Sciences [q-bio], Retinoic acid, Gene Expression, DNA Methyltransferase 3A, Epigenesis, Genetic, chemistry.chemical_compound, Mice, 0302 clinical medicine, cytokine, DNA (Cytosine-5-)-Methyltransferases, gène régulateur, transcription génique, EZH2, Epigenetic, Cell Differentiation, santé humaine, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, néoplasme, 3. Good health, [SDV] Life Sciences [q-bio], Gene Expression Regulation, Neoplastic, HOXB4, Histone, Oncology, 030220 oncology & carcinogenesis, DNMT3A, miR-10a, atypical myeloproliferative neoplasms, epigenetic, Female, Stem cell, Research Article, expression des gènes, Genotype, Biology, lcsh:RC254-282, Leukemoid Reaction, 03 medical and health sciences, Cell Line, Tumor, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, microRNA, Genetics, Animals, Humans, Epigenetics, Atypical myeloproliferative neoplasms, Progenitor cell, Cell Proliferation, Homeodomain Proteins, Myeloproliferative Disorders, Hematopoietic Stem Cells, MicroRNAs, 030104 developmental biology, DNA demethylation, chemistry, Article RECHERCHE, Case-Control Studies, Mutation, Cancer research, biology.protein, Biomarkers, Transcription Factors
الوصف: Background Atypical Myeloproliferative Neoplasms (aMPN) share characteristics of MPN and Myelodysplastic Syndromes. Although abnormalities in cytokine signaling are common in MPN, the pathophysiology of atypical MPN still remains elusive. Since deregulation of microRNAs is involved in the biology of various cancers, we studied the miRNome of aMPN patients. Methods MiRNome and mutations in epigenetic regulator genes ASXL1, TET2, DNMT3A, EZH2 and IDH1/2 were explored in aMPN patients. Epigenetic regulation of miR-10a and HOXB4 expression was investigated by treating hematopoietic cell lines with 5-aza-2’deoxycytidine, valproic acid and retinoic acid. Functional effects of miR-10a overexpression on cell proliferation, differentiation and self-renewal were studied by transducing CD34+ cells with lentiviral vectors encoding the pri-miR-10a precursor. Results MiR-10a was identified as the most significantly up-regulated microRNA in aMPN. MiR-10a expression correlated with that of HOXB4, sitting in the same genomic locus. The transcription of these two genes was increased by DNA demethylation and histone acetylation, both necessary for optimal expression induction by retinoic acid. Moreover, miR-10a and HOXB4 overexpression seemed associated with DNMT3A mutation in hematological malignancies. However, overexpression of miR-10a had no effect on proliferation, differentiation or self-renewal of normal hematopoietic progenitors. Conclusions MiR-10a and HOXB4 are overexpressed in aMPN. This overexpression seems to be the result of abnormalities in epigenetic regulation mechanisms. Our data suggest that miR-10a could represent a simple marker of transcription at this genomic locus including HOXB4, widely recognized as involved in stem cell expansion. Electronic supplementary material The online version of this article (10.1186/s12885-018-4993-2) contains supplementary material, which is available to authorized users.
وصف الملف: application/pdf
اللغة: English
تدمد: 1471-2407
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5912d230c444fcfc74e9a26e165b969e
http://link.springer.com/article/10.1186/s12885-018-4993-2
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....5912d230c444fcfc74e9a26e165b969e
قاعدة البيانات: OpenAIRE
الوصف
تدمد:14712407