1. Impaired expression of DICER and some microRNAs in HBZ expressing cells from acute adult T-cell leukemia patients.
- Author
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Gazon H, Belrose G, Terol M, Meniane JC, Mesnard JM, Césaire R, and Peloponese JM Jr
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Basic-Leucine Zipper Transcription Factors metabolism, CD4-Positive T-Lymphocytes drug effects, CD4-Positive T-Lymphocytes metabolism, CD4-Positive T-Lymphocytes virology, Cell Line, Tumor, DEAD-box RNA Helicases metabolism, Female, Gene Expression Regulation, Leukemic drug effects, HEK293 Cells, HTLV-I Infections drug therapy, HTLV-I Infections virology, Human T-lymphotropic virus 1 genetics, Human T-lymphotropic virus 1 metabolism, Human T-lymphotropic virus 1 physiology, Humans, Jurkat Cells, Leukemia-Lymphoma, Adult T-Cell drug therapy, Leukemia-Lymphoma, Adult T-Cell virology, Male, Middle Aged, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma virology, Proto-Oncogene Proteins c-jun genetics, Proto-Oncogene Proteins c-jun metabolism, Retroviridae Proteins metabolism, Ribonuclease III metabolism, Valproic Acid administration & dosage, Basic-Leucine Zipper Transcription Factors genetics, DEAD-box RNA Helicases genetics, HTLV-I Infections genetics, Leukemia-Lymphoma, Adult T-Cell genetics, MicroRNAs genetics, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma genetics, Retroviridae Proteins genetics, Ribonuclease III genetics
- 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., Competing Interests: CONFLICT OF INTERESTS None of the authors have competing interests
- Published
- 2016
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