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      Circulating microRNA: a novel potential biomarker for early diagnosis of Intracranial Aneurysm Rupture a case control study

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          Abstract

          Objective

          To investigate warning effect of serum miRNA for intracranial aneurysm rupture through microarray hybridization.

          Methods

          24 were selected from 560 patients in our department and divided into group A, B, C and D. They are aneurysms with daughter aneurysms group, aneurysm without daughter aneurysms group, ruptured aneurysms group and angiography negative group. Then a microarray study was carried out using serum miRNA. Differentially expressed miRNAs were identified. Cluster analysis was performed in order to make the results looks more intuitive and potential gene targets were retrieved from miRNA target prediction databases.

          Results

          Microarray study identified 86 miRNAs with significantly different (p < 0.05) expression levels between three experimental groups and control group. Among them 69 are up-regulated and 17 are down-regulated. All miRNAs in group A are up-regulated, while there are up and down-regulated in group B and C. A total of 8291 predicted target genes are related to these miRNAs. Bioinformatic analysis revealed that several target genes are involved in apoptosis and activation of cells associated with function of vascular wall.

          Conclusion

          Our gene level approach reveals several different serum miRNAs between normal people and aneurysm patients, as well as among different phases of aneurysm, suggesting that miRNA may participate in the regulation of the occurrence and development of intracranial aneurysm, and also have warning effect for intracranial aneurysm rupture. All differently expressed miRNA in group A are up-regulated, which may suggesting protective function of miRNA for intracranial vascular wall.

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          Most cited references16

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          The role of microRNA genes in papillary thyroid carcinoma.

          Apart from alterations in the RET/PTC-RAS-BRAF pathway, comparatively little is known about the genetics of papillary thyroid carcinoma (PTC). We show that numerous microRNAs (miRNAs) are transcriptionally up-regulated in PTC tumors compared with unaffected thyroid tissue. A set of five miRNAs, including the three most up-regulated ones (miR-221, -222, and -146), distinguished unequivocally between PTC and normal thyroid. Additionally, miR-221 was up-regulated in unaffected thyroid tissue in several PTC patients, presumably an early event in carcinogenesis. Tumors in which the up-regulation (11- to 19-fold) of miR-221, -222, and -146 was strongest showed dramatic loss of KIT transcript and Kit protein. In 5 of 10 such cases, this down expression was associated with germline single-nucleotide changes in the two recognition sequences in KIT for these miRNAs. We conclude that up-regulation of several miRs and regulation of KIT are involved in PTC pathogenesis, and that sequence changes in genes targeted by miRNAs can contribute to their regulation.
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            MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation.

            MicroRNAs (miRNAs) are a recently discovered class of endogenous, small, noncoding RNAs that regulate about 30% of the encoding genes of the human genome. However, the role of miRNAs in vascular disease is currently completely unknown. Using microarray analysis, we demonstrated for the first time that miRNAs are aberrantly expressed in the vascular walls after balloon injury. The aberrantly expressed miRNAs were further confirmed by Northern blot and quantitative real-time polymerase chain reaction. Modulating an aberrantly overexpressed miRNA, miR-21, via antisense-mediated depletion (knock-down) had a significant negative effect on neointimal lesion formation. In vitro, the expression level of miR-21 in dedifferentiated vascular smooth muscle cells was significantly higher than that in fresh isolated differentiated cells. Depletion of miR-21 resulted in decreased cell proliferation and increased cell apoptosis in a dose-dependent manner. MiR-21-mediated cellular effects were further confirmed in vivo in balloon-injured rat carotid arteries. Western blot analysis demonstrated that PTEN and Bcl-2 were involved in miR-21-mediated cellular effects. The results suggest that miRNAs are novel regulatory RNAs for neointimal lesion formation. MiRNAs may be a new therapeutic target for proliferative vascular diseases such as atherosclerosis, postangioplasty restenosis, transplantation arteriopathy, and stroke.
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              The roles of microRNA in cancer and apoptosis.

              microRNAs (miRNAs) are highly conserved, non-protein-coding RNAs that function to regulate gene expression. In mammals this regulation is primarily carried out by repression of translation. miRNAs play important roles in homeostatic processes such as development, cell proliferation and cell death. Recently the dysregulation of miRNAs has been linked to cancer initiation and progression, indicating that miRNAs may play roles as tumour suppressor genes or oncogenes. The role of miRNAs in apoptosis is not fully understood, however, evidence is mounting that miRNAs are important in this process. The dysregulation of miRNAs involved in apoptosis may provide a mechanism for cancer development and resistance to cancer therapy. This review examines the biosynthesis of miRNA, the mechanisms of miRNA target regulation and the involvement of miRNAs in the initiation and progression of human cancer. It will include miRNAs involved in apoptosis, specifically those miRNAs involved in the regulation of apoptotic pathways and tumour suppressor/oncogene networks. It will also consider emerging evidence supporting a role for miRNAs in modulating sensitivity to anti-cancer therapy.
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                Author and article information

                Contributors
                Journal
                J Transl Med
                J Transl Med
                Journal of Translational Medicine
                BioMed Central
                1479-5876
                2013
                27 November 2013
                : 11
                : 296
                Affiliations
                [1 ]Department of interventional neuroradiology Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, 6, Tiantan Xili, Chongwen, Beijing, 100050, P.R. China
                [2 ]Department of neurosurgery, The First Hospital of Shijiazhuang City, 36, Fanxi Road, Changan District, Shijiazhuang city, P.R. China
                Article
                1479-5876-11-296
                10.1186/1479-5876-11-296
                4222264
                24279374
                b8f30bd5-b955-4047-823c-28eb30ca8c25
                Copyright © 2013 Jin et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 6 July 2013
                : 5 November 2013
                Categories
                Research

                Medicine
                intracranial aneurysm,serum mirna,microarray analysis
                Medicine
                intracranial aneurysm, serum mirna, microarray analysis

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