MicroRNAs　(miRNAs)　regulate　gene　expression　and　may　contribute　to　HIV-1　infection.　In　this　study,　our　goal　was　to　investigate　the　mechanisms　by　which　miR-34a　influenced　Tat-induced　HIV-1　trans-activation　through　the　SIRT1/NF　kappa　B　pathway.　We　showed　that　Tat　induced　up-regulation　of　miR-34a　expression　in　TZM-bl　cells.　MiR-34a　significantly　inhibited　SIRT1　expression.　Overexpression　of　miR-34a　increased　Tat-induced　LTR　transactivation.　Forced　expression　of　miR-34a　decreased　SIRT1　protein　expression　and　consequently　diminished　Tat-induced　acetylation　of　p65,　while　treatment　with　a　miR-34a　inhibitor　had　the　opposite　effect.　These　results　suggest　that　regulating　SIRT1　by　down-regulation　of　miR-34a　levels　may　be　a　therapeutic　strategy　against　HIV-1　replication.　(C)　2012　Federation　of　European　Biochemical　Societies.　Published　by　Elsevier　B.　V.　All　rights　reserved.