Latency-Associated Transcript-Derived MicroRNAs in Herpes Simplex Virus Type 1 Target SMAD3 and SMAD4 in TGF-β/Smad Signaling Pathway.

Background: During its latent infection, hepatic stellate cell (HSV-1) produces only a micro RNA (miRNA) precursor called latency-associated transcript (LAT), which encodes six distinct miRNAs. Recent studies have suggested that some of these miRNAs could target cellular mRNAs. One of the key cell s...

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Publicado en:Iranian Biomedical Journal Vol. 25; no. 3; pp. 169 - 180
Autores principales: Shojaei Jeshvaghani, Zahra, Arefian, Ehsan, Asgharpour, Sara, Soleimani, Masoud
Formato: research Journal Article
Publicado: Pasteur Institute of Iran May2021
Acceso en línea:Ver este registro en EBSCOhost
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      dt: May2021
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      pub: Pasteur Institute of Iran
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        10.52547/ibj.25.3.169
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        atl: Latency-Associated Transcript-Derived MicroRNAs in Herpes Simplex Virus Type 1 Target SMAD3 and SMAD4 in TGF-β/Smad Signaling Pathway.
      aug:
        au:
          Shojaei Jeshvaghani, Zahra
          Arefian, Ehsan
          Asgharpour, Sara
          Soleimani, Masoud
        affil: Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran
      sug:
        subj:
          Herpesviruses
          RNA Metabolism
          Growth Substances Metabolism
          Carrier Proteins Metabolism
          Signal Transduction
          Cell Physiology
          RNA
          Genes
          Nucleotides
          Epithelial Cells
      ab: Background: During its latent infection, hepatic stellate cell (HSV-1) produces only a micro RNA (miRNA) precursor called latency-associated transcript (LAT), which encodes six distinct miRNAs. Recent studies have suggested that some of these miRNAs could target cellular mRNAs. One of the key cell signaling pathways that can be affected by HSV-1 is the TGF-β/Smad pathway. Herein, we investigated the potential role of the LAT as well as three LAT-derived miRNAs in targeting SMAD3 and SMAD4, as two main mediators in TGF-β/Smad.Methods: The selection of LAT-derived miRNAs was based on the search results obtained from an online miRNA prediction tool. HEK293T cells were transfected with each miRNA-expressing lentivector and with the construct-expressing LAT. To survey the effect of LAT on the expression of pro-fibrotic markers, we transfected LX-2 cells with LAT construct. The impact of viral miRNA overexpression on SMADs and fibrotic markers was measured by quantitative PCR and luciferase assays.Results: Among the LAT-derived miRNAs, miR-H2, miR-H3, and miR-H4 were selected for the study. Our results demonstrated that while miR-H2 binds to both SMAD mRNAs, miR-H3 and miR-H4 inhibit only the expression of the SMAD4 and SMAD3, respectively. Transfection of the LX-2 with LAT also decreased pro-fibrotic genes expression.Conclusion: Our findings display that LAT negatively regulates TGF-β/Smad through targeting SMAD3 and SMAD4 by its miRNAs. These viral miRNAs can also contribute to the development of therapeutic interventions in diseases for which prevention or treatment can be achieved through targeting TGF-β pathway.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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