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JCR 2016
جستجوی مقالات
شنبه 29 آذر 1404
Iranian Biomedical Journal
، جلد ۲۵، شماره ۳، صفحات ۱۶۹-۱۷۹
عنوان فارسی
چکیده فارسی مقاله
کلیدواژههای فارسی مقاله
عنوان انگلیسی
Latency-Associated Transcript-Derived MicroRNAs in Herpes Simplex Virus Type 1 Target SMAD3 and SMAD4 in TGF-β/Smad Signaling Pathway
چکیده انگلیسی مقاله
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.
کلیدواژههای انگلیسی مقاله
Herpesvirus 1, Latency associated transcript, microRNAs, SMAD3 protein, SMAD4 protein
نویسندگان مقاله
| Zahra Shojaei Jeshvaghani
Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran
| Masoud Soleimani
Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran
| Sara Asgharpour
Stem Cell Technology Research Center, Tehran, Iran
| Ehsan Arefian
Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
نشانی اینترنتی
http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-2346-1&slc_lang=en&sid=1
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en
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