title: Down-regulation of NAMPT expression by miR-182 is involved in Tat-induced HIV-1 long terminal repeat (LTR) transactivation.
abstract: 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 TZM-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.
authors.affiliation: College of Life Science & Bioengineering, Beijing University of Technology, Pingleyuan 100#, District of Chaoyang, Beijing 100124, China.
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Chen
authors.forename: Hong-Sheng
authors.initials: HS
authors.lastname: Zhang
authors.forename: Tong-Chao
authors.initials: TC
authors.lastname: Wu
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Sang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ruan
mesh_terms: D020413:3' Untranslated Regions; D000107:Acetylation; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D015870:Gene Expression; D015967:Gene Expression Regulation, Viral; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics* / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D015533:Transcriptional Activation; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000502:physiology*
chemical_list: D020413:3' Untranslated Regions; D016207:Cytokines; D035683:MicroRNAs; C538984:Mirn182 microRNA, human; C498143:RELA protein, human; D051996:Transcription Factor RelA; D054322:tat Gene Products, Human Immunodeficiency Virus; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human; C447939:SIRT1 protein, human; D056564:Sirtuin 1