title: Impaired expression of DICER and some microRNAs in HBZ expressing cells from acute adult T-cell leukemia patients.
abstract: Global dysregulation of microRNAs (miRNAs), a class of non-coding RNAs that regulate genes expression, is a common feature of human tumors. Profiling of cellular miRNAs on Adult T cell Leukemia (ATL) cells by Yamagishi et al. showed a strong decrease in expression for 96.7% of cellular miRNAs in ATL cells. However, the mechanisms that regulate the expression of miRNAs in ATL cells are still largely unknown. In this study, we compared the expression of 12 miRs previously described for being overexpress by Tax and the expression of several key components of the miRNAs biogenesis pathways in different HBZ expressing cell lines as well as in primary CD4 (+) cells from acute ATL patients. We showed that the expression of miRNAs and Dicer1 were downregulated in cells lines expressing HBZ as well as in fresh CD4 (+) cells from acute ATL patients. Using qRT-PCR, western blotting analysis and Chromatin Immunoprecipitation, we showed that dicer transcription was regulated by c-Jun and JunD, two AP-1 transcription factors. We also demonstrated that HBZ affects the expression of Dicer by removing JunD from the proximal promoter. Furthermore, we showed that at therapeutic concentration of 1mM, Valproate (VPA) an HDAC inhibitors often used in cancer treatment, rescue Dicer expression and miRNAs maturation. These results might offer a rationale for clinical studies of new combined therapy in an effort to improve the outcome of patients with acute ATL.
authors: CPBS, CNRS UMR 5236, Université Montpellier 1, Montpellier, France.|Laboratoire de Virologie-Immunologie JE2503, Centre Hospitalier et Universitaire de Martinique, Fort de France, Martinique.
authors: Hélène
authors: H
authors: Gazon
authors: Laboratoire de Virologie-Immunologie JE2503, Centre Hospitalier et Universitaire de Martinique, Fort de France, Martinique.
authors: Gildas
authors: G
authors: Belrose
authors: CPBS, CNRS UMR 5236, Université Montpellier 1, Montpellier, France.|Laboratoire de Virologie-Immunologie JE2503, Centre Hospitalier et Universitaire de Martinique, Fort de France, Martinique.
authors: Marie
authors: M
authors: Terol
authors: Service Hématologie Clinique, Centre Hospitalier et Universitaire de Martinique, Fort de France, Martinique.
authors: Jean-Come
authors: JC
authors: Meniane
authors: CPBS, CNRS UMR 5236, Université Montpellier 1, Montpellier, France.
authors: Jean-Michel
authors: JM
authors: Mesnard
authors: Laboratoire de Virologie-Immunologie JE2503, Centre Hospitalier et Universitaire de Martinique, Fort de France, Martinique.
authors: Raymond
authors: R
authors: Césaire
authors: CPBS, CNRS UMR 5236, Université Montpellier 1, Montpellier, France.
authors: Jean-Marie
authors: JM
authors: Peloponese
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D045744:Cell Line, Tumor; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D057809:HEK293 Cells; D015490:HTLV-I Infections / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D012191:Retroviridae Proteins / Q000235:genetics* / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics* / Q000378:metabolism; D014635:Valproic Acid / Q000008:administration & dosage
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C479751:HBZ protein, human T-cell leukemia virus type I; C559371:JunD protein, human; D035683:MicroRNAs; D016755:Proto-Oncogene Proteins c-jun; D012191:Retroviridae Proteins; D014635:Valproic Acid; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: AP-1; Dicer; HBZ; JunD; miRNAs