MicroRNAs in the interaction between host and bacterial pathogens

Sahu

et al. 2015

Cell Host & Microbe

224

193

The outcome of the interaction between Mycobacterium tuberculosis (Mtb) and a macrophage depends on the interplay between host defense and bacterial immune subversion mechanisms. MicroRNAs critically regulate several host defense mechanisms, but their role in the Mtb-macrophage interplay remains unclear. MicroRNA profiling of Mtb-infected macrophages revealed the downregulation of miR-let-7f in a manner dependent on the Mtb secreted effector ESAT-6. We establish that let-7f targets A20, a feedback inhibitor of the NF-κB pathway. Expression of let-7f decreases and A20 increases with progression of Mtb infection in mice. Mtb survival is attenuated in A20-deficient macrophages, and the production of TNF, IL-1β, and nitrite, which are mediators of immunity to Mtb, is correspondingly increased. Further, let-7f overexpression diminishes Mtb survival and augments the production of cytokines including TNF and IL-1β. These results uncover a role for let-7f and its target A20 in regulating immune responses to Mtb and controlling bacterial burden.

Section: Introductionmentioning

confidence: 99%

MicroRNA let-7 Modulates the Immune Response to Mycobacterium tuberculosis Infection via Control of A20, an Inhibitor of the NF-κB Pathway

Sahu

et al. 2015

Cell Host & Microbe

224

193

“…Through the combined screening of mouse miRNA mimic and inhibitor libraries, Santhakumar and coworkers 32 identified miRNAs with broad antiviral activity against virus representatives of all three herpesvirus families, specifically herpes simplex virus 1, murine cytomegalovirus, and murine gamma herpesvirus 68. Although it is well established that bacterial pathogens cause extensive changes in the miRNome of host cells, [54][55][56] until recently the role of miRNAs during infection by bacterial pathogens had not been addressed on a systematic, genome-wide scale. To tackle this issue, we performed a phenotypic high-content screening using a library of miRNA mimics to identify novel modulators of infection by S. Typhimurium, 33 an extensively studied Gram-negative pathogen and a main causative agent of foodborne illnesses.…”

Section: V12mentioning

confidence: 99%

MicroRNA Screening and the Quest for Biologically Relevant Targets

Eulálio

Mano

2015

SLAS Discovery

Self Cite

MicroRNAs (miRNAs) are a class of genome-encoded small RNAs that post-transcriptionally regulate gene expression by repressing target transcripts containing partially or fully complementary binding sites.Despite their relatively low number, miRNAs have been shown to directly regulate a large fraction of the transcriptome. In agreement with their pervasive role in the regulation of eukaryotic gene expression, miRNAs have been implicated in virtually all biological processes, including different pathologies.The use of screening technologies to systematically analyze miRNA function in cell-based assays offers a unique opportunity to gain new insights into complex biological and disease-relevant processes. Given the low complexity of the miRNome and the similarities to small interfering RNA (siRNA) screening experimental approaches, phenotypic screening using genome-wide libraries of miRNA mimics or inhibitors is not, per se, technically challenging. The identification of miRNA targets and, more importantly, the characterization of their mechanisms of action through the identification of the key targets underlying observed phenotypes remain the major challenges of this approach.This article provides an overview of cell-based screenings for miRNA function that were performed in different biological contexts. The advantages and limitations of computational and experimental approaches commonly used to identify miRNA targets are also discussed.

“…According to the latest update, 2,578 unique mature miRNAs are currently annotated in the human genome [3] and participate in the regulation of multiple events, such as cellular proliferation or apoptosis. For this reason, it is expected to find different and tightly regulated expression levels among the cellular miRNAs, depending on the cellular program [4].…”

Section: Introductionmentioning

confidence: 99%

Is HERV-K and HERV-W Expression Regulated by miR-155 in Kidney Transplant Patients with Human Cytomegalovirus Infection?

et al. 2018

According to the latest update, 2,578 unique mature microRNAs (miRNAs) are currently annotated in the human genome and participate in the regulation of multiple events, such as cellular proliferation or apoptosis. A previous study analyzing global miRNA expression patterns in GH cells (high human endogenous retrovirus, HERV, K vs. low) showed that 2 miRNAs (miR-663 and miR-638) are differentially regulated and exhibit expression parallel to that of HERV-K. The aim of this study was to evaluate HERV-K and -W pol gene and miR-155 expression in kidney transplant recipients and the possible relationship between them. The comparison between kidney transplant patients negative for human cytomegalovirus (HCMV) infection and positive patients showed a significant difference in terms of miR-155 expression (p = 0.0111). We demonstrated that HERV-K and -W pol gene expression was significantly higher in CMV-infected kidney transplant recipients versus those not infected as previously reported by our groups. Our correlation data suggest that miR-155 are not directly involved in regulating the HERV notwithstanding that we together observed increased expression of HERV-K and -W and diminished expression of miR-155 in HCMV-infected human kidney transplant recipients.