MiR‐34a is involved in Tat‐induced HIV‐1 long terminal repeat (LTR) transactivation through the SIRT1/NFκB pathway

Abstract

a b s t r a c tMicroRNAs (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 transactivation through the SIRT1/NFjB 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.

Dysregulated miR-34a–SIRT1–Acetyl p65 Axis Is a Potential Mediator of Immune Activation in the Colon during Chronic Simian Immunodeficiency Virus Infection of Rhesus Macaques

“…These findings demonstrate activation of DDR signaling and represent a potential mechanism triggering and driving miR-34a upregulation. In addition, the viral protein (HIV/SIV Tat) was also shown to induce the expression of miR-34a (43-44). Therefore, it is likely that Tat protein (direct effects of viral replication) and oxidative stress induced DDR (indirect effects of viral replication) can separately or collectively upregulate miR-34a expression in the colonic epithelium and LPL compartments.…”

miR-190b Is Markedly Upregulated in the Intestine in Response to Simian Immunodeficiency Virus Replication and Partly Regulates Myotubularin-Related Protein-6 Expression

“…Recent studies have attributed more significant roles for these small RNA molecules in regulating the immune response that includes immune cell development, proliferation, activation and differentiation (18,22-26). Further, several in vitro studies clearly show that HIV and the host miRNA machinery crisscross at several post transcriptional levels (27-31). The restraints exerted by the host miRNA machinery on HIV replication is clearly evident from the finding that viral replication kinetics are enhanced in peripheral blood mononuclear cells following siRNA mediated knockdown of Drosha and Dicer (32).…”

Heat stress: A risk factor for skin carcinogenesis

“…SCC accounts for 20% of all cutaneous cancers; it is the second most common skin cancer after BCC Sridhar et al, 2012). The incidence of SCC varies in different countries, but the US and Australia have the highest reported incidence, this being 20% of all skin cancer cases (Zhang et al, 2012). This cancer is two to three times more common in men than in women, and mostly affects adults over sixty years of age, though in recent years, the incidence of SCC in people below fifty years of age has increased (Monroe et al, 2011;Sabunciyan et al, 2015).…”