• 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • IRF expression had previously been described as


    IRF1 expression had previously been described as a factor that contributes to susceptibility for HIV-1 infection [14]. Our findings evidenced a different expression modulation of this transcription factor in the two groups of DC according with the expression of the important Th1 driving cytokine IL-12 (Fig. 2), emphasizing once more that genomic profile could told us a hide tale about DC functionality. The emerging role of IL-18 in the pathogenesis of HIV infection has been recently described, suggesting that IL-18 could be protective against HIV replication [17]. IL-18 plays an important role in DC biology, being necessary for induction of effector T zip inhibitor [18] and memory CD8+ T cells [19]. Moreover it has been reported that in DC augmented level of IL-18 inversely correlated with IL-10 [20], as observed also in our results (Table 3). In our study, possibly due to the small size of studied individuals, and we are aware of this limitation, the observed differences in genes expression did not lead to statistically significant differences in commonly used markers of DC maturation, activation and in vitro ability to induced IFN-γ+ T cells.
    Conclusions All together these findings pointed out that actual criteria for the selection of HIV+ individuals for immunotherapy (mainly PVL, CD4+ and CD8+ counts) are not ensuring a similar vaccine product in term of genomic activation of monocyte-derived DC. Further investigations are needed to elucidate the discrepancy between expression profiles in DC from different donors.
    Competing interests
    Authors\' contributions
    Acknowledgements This work was supported by the São Paulo Research foundation (FAPESP) (2013/06142-1 and 2012/18879-6), Brazilian National Council for Research (CNPq) (473216/2012-4) and MCT/CNPq/MEC/CAPES Casadinho/Procad (552195/2011-1). E.C.R. is recipient of a Fellowship from Proex-CAPES. L.T.S. is recipient of a Fellowship from FAPESP. A.P. and S.C. are recipient of a Fellowship from CNPq. We thank Dr. Alexandre De Almeida (Faculty of Medicine, University of Sao Paulo, Brazil) for HIV+ patients\' recruitment; Prof. Helder T.I. Nakaya (Department of Clinical Analyses and Toxicology, University of Sao Paulo, Brazil) for helpful discussion. We wish to thanks all patients for the collaboration.
    Introduction MicroRNAs (miRNAs) are small non-coding single stranded RNAs (21–25 nucleotides) which negatively regulate gene expression by binding to imperfect complementary sites in the 3′ untranslated regions (3′ UTRs) of their mRNA targets [1]. Bioinformatics studies point out that a single miRNA can bind to numerous mRNA targets and therefore small alteration in expression of a specific miRNA may have pathological and physiological outcome [2]. The connection between miRNAs and cancer was firstly recognized in 2006 [3] among chronic lymphocytic leukemia patients. MiRNAs has a key role in cancer biology due to their function in the regulation of cellular processes, including growth, differentiation and apoptosis [4]. Point mutations in miRNA and mRNA sequences, loss or mutation in the promoter regions for specific miRNA clusters, and epigenetic changes may disrupt miRNA activity in cancer cells [5]. In addition, single nucleotide polymorphisms (SNPs) at the miRNA gene region (miR-SNPs) may alter miRNA expression and/or maturation [6–8]. In spite of existence of various reports for correlation between the SNPs and physiological events [9], few association studies have shown the miRNA related SNPs in complex disease such as cancer. Breast cancer (BC) is the second most commonly diagnosed malignancy worldwide and the most common kind of cancer among women in developed countries [10]. Recently, we identified genetic variants in the target site of mRNA and precursor miRNA sequence as possible biomarkers in BC [11,12]. In this study, we have investigated the possible association between hsa-mir-499a rs3746444 polymorphism (n.73A>G) and BC risks.