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      Characterisation of peripheral blood mononuclear cell microRNA in hepatitis B-related acute-on-chronic liver failure

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          Abstract

          Hepatitis B-related acute-on-chronic liver failure (HBV-ACLF) is a life-threatening condition and the mechanisms of its development and progression remain unclear. The aim of this study was to define the characteristics of peripheral blood mononuclear cell microRNAs in patients with HBV-ACLF. In this study, novel microRNA (miRNA) biomarkers of peripheral blood mononuclear cells (PBMCs) in patients with HBV-ACLF were characterised by high-throughput sequencing and validated by quantitative real-time polymerase chain reaction (qRT-PCR). The results showed 78 miRNAs were significantly differentially expressed in patients with HBV-ACLF compared to patients with chronic hepatitis B (CHB) and healthy controls. Among patients with HBV-ACLF, 17 dysregulated miRNAs increased or decreased more than 4-fold, of which eight miRNAs had higher expression levels than median level. qRT-PCR validation demonstrated that six miRNAs (hsa-miR-21-5p, hsa-miR-34c-5p, hsa-miR-143-3p, hsa-miR-143-5p, hsa-miR-374a-3p and hsa-miR-542-3p) may be useful as novel biomarkers for the diagnosis of HBV-ACLF. Five novel miRNAs (L-miR-1~5) were detected and two (L-miR-1 and L-miR-3) were significantly differentially expressed in patients with HBV-ACLF. Conclusions: The miRNA expression profile of PBMCs is altered in patients with HBV-ACLF, and a signature of six miRNAs may be a promising biomarker for HBV-ACLF progression.

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          Most cited references16

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          MicroRNA control of signal transduction.

          MicroRNAs (miRNAs) are integral elements in the post-transcriptional control of gene expression. After the identification of hundreds of miRNAs, the challenge is now to understand their specific biological function. Signalling pathways are ideal candidates for miRNA-mediated regulation owing to the sharp dose-sensitive nature of their effects. Indeed, emerging evidence suggests that miRNAs affect the responsiveness of cells to signalling molecules such as transforming growth factor-beta, WNT, Notch and epidermal growth factor. As such, miRNAs serve as nodes of signalling networks that ensure homeostasis and regulate cancer, metastasis, fibrosis and stem cell biology.
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            Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21.

            The tumor suppressor PDCD4 is a proinflammatory protein that promotes activation of the transcription factor NF-kappaB and suppresses interleukin 10 (IL-10). Here we found that mice deficient in PDCD4 were protected from lipopolysaccharide (LPS)-induced death. The induction of NF-kappaB and IL-6 by LPS required PDCD4, whereas LPS enhanced IL-10 induction in cells lacking PDCD4. Treatment of human peripheral blood mononuclear cells with LPS resulted in lower PDCD4 expression, which was due to induction of the microRNA miR-21 via the adaptor MyD88 and NF-kappaB. Transfection of cells with a miR-21 precursor blocked NF-kappaB activity and promoted IL-10 production in response to LPS, whereas transfection with antisense oligonucleotides to miR-21 or targeted protection of the miR-21 site in Pdcd4 mRNA had the opposite effect. Thus, miR-21 regulates PDCD4 expression after LPS stimulation.
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              miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions

              MicroRNAs (miRNAs) are small non-coding RNA molecules capable of negatively regulating gene expression to control many cellular mechanisms. The miRTarBase database (http://mirtarbase.mbc.nctu.edu.tw/) provides the most current and comprehensive information of experimentally validated miRNA-target interactions. The database was launched in 2010 with data sources for >100 published studies in the identification of miRNA targets, molecular networks of miRNA targets and systems biology, and the current release (2013, version 4) includes significant expansions and enhancements over the initial release (2010, version 1). This article reports the current status of and recent improvements to the database, including (i) a 14-fold increase to miRNA-target interaction entries, (ii) a miRNA-target network, (iii) expression profile of miRNA and its target gene, (iv) miRNA target-associated diseases and (v) additional utilities including an upgrade reminder and an error reporting/user feedback system.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                12 August 2015
                2015
                : 5
                : 13098
                Affiliations
                [1 ]State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine . 79 Qingchun Rd., Hangzhou, 310003. China
                [2 ]Systems Biology Division, Zhejiang-California International Nanosystems Institute, Zhejiang University.
                Author notes
                Article
                srep13098
                10.1038/srep13098
                4533317
                26267843
                a79f2860-b210-4886-b7f8-954218a6dfdd
                Copyright © 2015, Macmillan Publishers Limited

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 15 January 2015
                : 17 July 2015
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