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      Overexpression of miR-206 in osteosarcoma and its associated molecular mechanisms as assessed through TCGA and GEO databases

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          Abstract

          Osteosarcoma (OS) is a primary malignant bone tumor that predominantly occurs in adolescents. Different types of OS tumor are highly malignant, associated with a poor prognosis and are invasive with blood-vessel dissemination characteristics, thus affected patients are prone to early lung metastasis. MicroRNAs (miRNAs/miR) are small non-coding RNA molecules that act as oncogenes or tumor suppressors during tumor development. The present study investigated the role of miR-206 in OS development. Bioinformatics analysis demonstrated that miR-206 was upregulated in OS and thus may serve as a risk factor for cancer prognosis. Subsequently, in response to miR-206 overexpression, differentially expressed genes were screened and analyzed using the Database for Annotation, Visualization and Integrated Discovery, Gene Ontology enrichment analysis, the Kyoto Encyclopedia of Genes and Genomes pathways and protein-protein interaction network construction, in order to identify key miR-206 targets. The results demonstrated that high miR-206 expression inhibited OS cell proliferation, which was associated with a good patient prognosis. Thus, miR-206 may serve as a potential target for OS treatment, in order to improve early disease diagnosis.

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          Most cited references51

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          Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs.

          MicroRNAs (miRNAs) are a class of noncoding RNAs that post-transcriptionally regulate gene expression in plants and animals. To investigate the influence of miRNAs on transcript levels, we transfected miRNAs into human cells and used microarrays to examine changes in the messenger RNA profile. Here we show that delivering miR-124 causes the expression profile to shift towards that of brain, the organ in which miR-124 is preferentially expressed, whereas delivering miR-1 shifts the profile towards that of muscle, where miR-1 is preferentially expressed. In each case, about 100 messages were downregulated after 12 h. The 3' untranslated regions of these messages had a significant propensity to pair to the 5' region of the miRNA, as expected if many of these messages are the direct targets of the miRNAs. Our results suggest that metazoan miRNAs can reduce the levels of many of their target transcripts, not just the amount of protein deriving from these transcripts. Moreover, miR-1 and miR-124, and presumably other tissue-specific miRNAs, seem to downregulate a far greater number of targets than previously appreciated, thereby helping to define tissue-specific gene expression in humans.
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            Diversifying microRNA sequence and function.

            MicroRNAs (miRNAs) regulate the expression of most genes in animals, but we are only now beginning to understand how they are generated, assembled into functional complexes and destroyed. Various mechanisms have now been identified that regulate miRNA stability and that diversify miRNA sequences to create distinct isoforms. The production of different isoforms of individual miRNAs in specific cells and tissues may have broader implications for miRNA-mediated gene expression control. Rigorously testing the many discrepant models for how miRNAs function using quantitative biochemical measurements made in vivo and in vitro remains a major challenge for the future.
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              The Gene Ontology (GO) project in 2006

              (2005)
              The Gene Ontology (GO) project () develops and uses a set of structured, controlled vocabularies for community use in annotating genes, gene products and sequences (also see ). The GO Consortium continues to improve to the vocabulary content, reflecting the impact of several novel mechanisms of incorporating community input. A growing number of model organism databases and genome annotation groups contribute annotation sets using GO terms to GO's public repository. Updates to the AmiGO browser have improved access to contributed genome annotations. As the GO project continues to grow, the use of the GO vocabularies is becoming more varied as well as more widespread. The GO project provides an ontological annotation system that enables biologists to infer knowledge from large amounts of data.
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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                March 2020
                08 January 2020
                08 January 2020
                : 19
                : 3
                : 1751-1758
                Affiliations
                Department of Orthopedic Surgery, The Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
                Author notes
                Correspondence to: Professor Bo Qiu, Department of Orthopedic Surgery, The Renmin Hospital of Wuhan University, 99 Zhang Zhidong Road, Wuhan, Hubei 430060, P.R. China, E-mail: qbtg163@ 123456163.com
                Article
                OL-0-0-11270
                10.3892/ol.2020.11270
                7039051
                7c9ddf4c-aeb4-4706-a443-ed4845be0b3b
                Copyright: © Xu et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 25 July 2019
                : 22 November 2019
                Categories
                Articles

                Oncology & Radiotherapy
                osteosarcoma,microrna-206,bioinformatics analysis,differentially expressed genes,survival analysis

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