Volume 11 Supplement 1

16th International Conference on Human Retroviruses: HTLV and Related Viruses

Open Access

Deregulation of RNAi silencing pathway by Human T-cell leukemia virus type 1 bZIP factor (HBZ)

  • Hélène Gazon1, 2, 3,
  • Jean-Michel Mesnard1, 2,
  • Raymond Césaire3 and
  • Jean-Marie PeloponeseJr1, 2Email author
Retrovirology201411(Suppl 1):O55

https://doi.org/10.1186/1742-4690-11-S1-O55

Published: 7 January 2014

Human T-cell leukemia virus type-1 (HTLV-1) is the causative agent of a non-Hodgkin leukemia known as adult T cell leukemia (ATL). MicroRNAs (miRNAs) are a class of non-coding RNAs that regulate the expression of target genes at posttranscriptional level. Biogenesis of miRNAs is tightly regulated and starts with the production of pri-miRNAs by RNA polymerase II. The pri-miRNAs are then cleaved by Drosha in conjunction with DGCR8 in the nucleus, generating pre-miRNAs, which are then transferred to the cytoplasm where Dicer1 further processes the hairpin into the mature miRNAs. With exception of few types of neoplasm, a general downregulation of miRNAs expression has been observed in cancers cells, mainly due to chromosomal abnormalities, epigenetic changes or aberrant expression of the miRNA biogenesis factors. Involvement of miRNAs alteration in the HTLV-1 life cycle has recently come to light. However, the mechanisms that regulate the expression of miRNAs biogenesis factors in ATL cells are still largely unknown. In this study, we assessed Dicer1 expression levels in ATL patients and investigated its transcriptional regulation in HTLV infected cell lines. We reported a significant correlation between reduced miRNA biogenesis and expression of HTLV-1 basic leucine zipper factor (HBZ). We showed that Dicer1 expression was downregulated in ATL patients vs. asymptomatic patients by qRT-PCR and western blot analysis. We also demonstrated that Dicer1 was regulated by AP-1 factors, through luciferase and Chip assays. Our data suggest that Dicer1 expression may be used as a promising prognostic marker and therapeutic target for ATL.

Authors’ Affiliations

(1)
CPBS, CNRS UMR 5236
(2)
CPBS, Université Montpellier 1
(3)
Laboratoire de Virologie-Immunologie, Centre Hospitalier et Universitaire de Fort de France

Copyright

© Gazon et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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