Journal
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
Volume 45, Issue 2, Pages 292-298Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2012.11.002
Keywords
miR-182; SIRT1; NAMPT; Tat; HIV-1
Categories
Funding
- National Natural Sciences Foundation of China [30800580]
- Beijing Natural Science Foundation [5112004, 5093025]
- Beijing Nova Program [2007B014]
- National Basic Research Program of China [2009CB930200]
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Tat's transactivating activity is controlled by sirtuin 1 (SIRT1) that connects HIV transcription with the metabolic state of the cell. Nicotinamide phosphoribosyltransferase (NAMPT) is a key enzyme in the salvaging pathway for the synthesis of nicotinamide adenine dinucleotide (NAD(+)) that is involved in energy metabolism. Host encoded microRNAs (miRNAs) may influence viral replication. In this study, our goal was aimed to investigate the regulation of miR-182 in TZM-bl cells and explore the mechanisms by which miR-182 influenced Tat-induced HIV-1 transactivation through targeting at down-regulation of NAMPT expression. We showed that miR-182 was up-regulated when Tat was expressed in T2M-bl cells. MiR-182 significantly inhibited NAMPT protein expression by acting on the 3'-UTR of the NAMPT mRNA. MiR-182 was involved in Tat-induced NAD(+) depletion, down-regulation of SIRT1 protein expression and activity, increased acetylation of p65. Forced expression of miR-182 mimics increased Tat-induced LTR transactivation. Our results uncover previously unknown links between Tat and a specific host cell miRNA that targets NAMPT. Our results suggest that strategies to augment NAMPT protein expression by down-regulation of miR-182 may have therapeutic benefits to prevent HIV-1 replication. (C) 2012 Elsevier Ltd. All rights reserved.
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