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      Restoration of miR-1228* Expression Suppresses Epithelial-Mesenchymal Transition in Gastric Cancer

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          Abstract

          Dysregulated miRNAs play critical roles during carcinogenesis and cancer progression. In the present study, the function of miR-1228* in regulating cancer progression was investigated in gastric cancer. Decreased expression of miR-1228* was observed in human gastric cancer tissues comparing to normal tissues. Subsequently, the role of miR-1228* was evaluated in vivo using the tumor xenograft model. In this model, miR-1228* overexpression suppressed xenograft tumor formation. Furthermore, we demonstrated miR-1228* negatively regulated NF-κB activity in SGC-7901 gastric cancer cells and found that CK2A2 was a target of miR-1228*. Upregulation of miR-1228* decreased the expression of mesenchymal markers and increased the epithelial marker E-cadherin, suggesting its potential role in suppressing epithelial-mesenchymal transition. Collectively, these findings provide the first evidence that miR-1228* plays an important role in regulating gastric cancer growth and suggest that selective restoration of miR-1228* might be beneficial for gastric cancer therapy.

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          Most cited references38

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          Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites

          mirSVR is a new machine learning method for ranking microRNA target sites by a down-regulation score. The algorithm trains a regression model on sequence and contextual features extracted from miRanda-predicted target sites. In a large-scale evaluation, miRanda-mirSVR is competitive with other target prediction methods in identifying target genes and predicting the extent of their downregulation at the mRNA or protein levels. Importantly, the method identifies a significant number of experimentally determined non-canonical and non-conserved sites.
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            Global cancer statistics

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              Genomic analysis of human microRNA transcripts.

              MicroRNAs (miRNAs) are important genetic regulators of development, differentiation, growth, and metabolism. The mammalian genome encodes approximately 500 known miRNA genes. Approximately 50% are expressed from non-protein-coding transcripts, whereas the rest are located mostly in the introns of coding genes. Intronic miRNAs are generally transcribed coincidentally with their host genes. However, the nature of the primary transcript of intergenic miRNAs is largely unknown. We have performed a large-scale analysis of transcription start sites, polyadenylation signals, CpG islands, EST data, transcription factor-binding sites, and expression ditag data surrounding intergenic miRNAs in the human genome to improve our understanding of the structure of their primary transcripts. We show that a significant fraction of primary transcripts of intergenic miRNAs are 3-4 kb in length, with clearly defined 5' and 3' boundaries. We provide strong evidence for the complete transcript structure of a small number of human miRNAs.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                12 March 2013
                : 8
                : 3
                : e58637
                Affiliations
                [1 ]Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, China
                [2 ]Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
                [3 ]Department of Gastroenterology, Tongde Hospital of Zhejiang Province, Hangzhou, China
                Sapporo Medical University, Japan
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: J. Cai LJ. Performed the experiments: LJ JW LZ J. Chen DZ SX CX. Analyzed the data: J. Cai LJ LZ. Contributed reagents/materials/analysis tools: J. Cai LJ JW. Wrote the paper: LJ J. Cai.

                Article
                PONE-D-12-33088
                10.1371/journal.pone.0058637
                3595239
                23554909
                0a93f25a-7aa6-4def-b31a-ab4919455b6d
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 25 October 2012
                : 5 February 2013
                Page count
                Pages: 9
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Biology
                Model Organisms
                Animal Models
                Mouse
                Medicine
                Gastroenterology and Hepatology
                Gastrointestinal Cancers
                Oncology
                Basic Cancer Research
                Tumor Physiology
                Cancer Detection and Diagnosis
                Early Detection
                Cancer Treatment
                Epigenetic Therapy
                Gene Therapy
                Cancers and Neoplasms
                Gastrointestinal Tumors

                Uncategorized
                Uncategorized

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