1. Mir-194-5p/BCLAF1 deregulation in AML tumorigenesis
- Author
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Lucia Altucci, S. Minucci, Concetta Ingenito, Isabella Pallavicini, Loredana D’Amato, V Belsito Petrizzi, A. Di Costanzo, Carmela Dell'Aversana, Sadia Saeed, Filomena Matarese, Annamaria Carissimo, G Lania, Hendrik G. Stunnenberg, Joost H.A. Martens, Cristina Giorgio, Dell'Aversana, C., Giorgio, C, D'Amato, L., Lania, G., Matarese, F., Saeed, S., Di Costanzo, A., Belsito Petrizzi, V., Ingenito, C., Martens, J. H. A., Pallavicini, I., Minucci, S., Carissimo, A., Stunnenberg, H. G., and Altucci, Lucia
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0301 basic medicine ,Cancer Research ,Myeloid ,medicine.drug_class ,Cellular differentiation ,Down-Regulation ,Apoptosis ,Biology ,medicine.disease_cause ,Acute myeloid leukaemia ,03 medical and health sciences ,Cancer epigenetics ,Cell Line, Tumor ,miR-194-5p/BCLAF1 ,microRNA ,medicine ,Humans ,Molecular Biology ,Oncogenesis ,Regulation of gene expression ,Tumor Suppressor Proteins ,Cell Cycle ,Histone deacetylase inhibitor ,Myeloid leukemia ,Cell Differentiation ,Hematology ,3. Good health ,Repressor Proteins ,Leukemia, Myeloid, Acute ,MicroRNAs ,Haematopoiesis ,Anesthesiology and Pain Medicine ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,Oncology ,miRNAs ,Immunology ,Cancer research ,Original Article ,Erratum ,Carcinogenesis - Abstract
Contains fulltext : 168891.pdf (Publisher’s version ) (Open Access) Deregulation of epigenetic mechanisms, including microRNA, contributes to leukemogenesis and drug resistance by interfering with cancer-specific molecular pathways. Here, we show that the balance between miR-194-5p and its newly discovered target BCL2-associated transcription factor 1 (BCLAF1) regulates differentiation and survival of normal hematopoietic progenitors. In acute myeloid leukemias this balance is perturbed, locking cells into an immature, potentially /`immortal/' state. Enhanced expression of miR-194-5p by treatment with the histone deacetylase inhibitor SAHA or by exogenous miR-194-5p expression re-sensitizes cells to differentiation and apoptosis by inducing BCLAF1 to shuttle between nucleus and cytosol. miR-194-5p/BCLAF1 balance was found commonly deregulated in 60 primary acute myeloid leukemia patients and was largely restored by ex vivo SAHA treatment. Our findings link treatment responsiveness to re-instatement of miR-194-5p/BCLAF1 balance. 11 p.
- Published
- 2017
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