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            "title": "MicroRNA profiling for the identification of cancers with unknown primary tissue-of-origin",
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            "title": "mir-29 regulates Mcl-1 protein expression and apoptosis",
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            "abstractNote": "Cellular expression of Mcl-1, an anti-apoptotic Bcl-2 family member, is tightly regulated. Recently, Bcl-2 expression was shown to be regulated by microRNAs, small endogenous RNA molecules that regulate protein expression through sequence-specific interaction with messenger RNA. By analogy, we reasoned that Mcl-1 expression may also be regulated by microRNAs. We chose human immortalized, but non-malignant, H69 cholangiocyte and malignant KMCH cholangiocarcinoma cell lines for these studies, because Mcl-1 is dysregulated in cells with the malignant phenotype. By in silico analysis, we identified a putative target site in the Mcl-1 mRNA for the mir-29 family, and found that mir-29b was highly expressed in cholangiocytes. Interestingly, mir-29b was downregulated in malignant cells, consistent with Mcl-1 protein upregulation. Enforced mir-29b expression reduced Mcl-1 protein expression in KMCH cells. This effect was direct, as mir-29b negatively regulated the expression of an Mcl-1 3' untranslated region (UTR)-based reporter construct. Enforced mir-29b expression reduced Mcl-1 cellular protein levels and sensitized the cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) cytotoxicity. Transfection of non-malignant cells (that express high levels of mir-29) with a locked-nucleic acid antagonist of mir-29b increased Mcl-1 levels and reduced TRAIL-mediated apoptosis. Thus mir-29 is an endogenous regulator of Mcl-1 protein expression, and thereby, apoptosis.",
            "publicationTitle": "Oncogene",
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            "creatorSummary": "Munker and Calin",
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            "title": "MicroRNA profiling in cancer",
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                    "creatorType": "author",
                    "firstName": "Reinhold",
                    "lastName": "Munker"
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                {
                    "creatorType": "author",
                    "firstName": "George A",
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            "abstractNote": "The diagnosis of cancer has undergone major changes in the last 40 years. Once based purely on morphology, diagnosis has come to incorporate immunological, cytogenetic and molecular methods. Many cancers, especially leukaemias, are now defined by molecular markers. Gene expression profiling based on mRNA has led to further refinement of the classification and diagnosis of cancer. More recently, miRNAs (microRNAs), among other small non-coding RNA molecules, have been discovered and found to be major players in cell biology. miRNAs, having both oncogenic and tumour-suppressive functions, are dysregulated in many types of cancer. miRNAs also interfere with metastasis, apoptosis and invasiveness of cancer cells. In the present review, we discuss recent advances in miRNA profiling in human cancer. We discuss both frequent and rare tumour types and give an outlook on future developments.",
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            "date": "Aug 1, 2011",
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            "title": "p53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB2",
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            "abstractNote": "p53 suppresses tumor progression and metastasis. Epithelial-mesenchymal transition (EMT) is a key process in tumor progression and metastasis. The transcription factors ZEB1 and ZEB2 promote EMT. Here, we show that p53 suppresses EMT by repressing expression of ZEB1 and ZEB2. By profiling 92 primary hepatocellular carcinomas (HCCs) and 9 HCC cell lines, we found that p53 up-regulates microRNAs (miRNAs), including miR-200 and miR-192 family members. The miR-200 family members transactivated by p53 then repress ZEB1/2 expression. p53-regulated miR-192 family members also repress ZEB2 expression. Inhibition or overexpression of the miRNAs affects p53-regulated EMT by altering ZEB1 and ZEB2 expression. Our findings indicate that p53 can regulate EMT, and that p53-regulated miRNAs are critical mediators of p53-regulated EMT.",
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            "title": "MicroRNA let-7a: A potential marker for selection of paclitaxel in ovarian cancer management",
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                    "firstName": "Lingeng",
                    "lastName": "Lu"
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                    "firstName": "Luca",
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            "abstractNote": "<p>Objectives<br/>Let-7 is a family of small non-coding RNAs regulating the expression of many genes that control important cellular activities. Let-7 is shown in vitro to sensitize cancer cells to platinum, but induce ovarian cancer resistance to paclitaxel. This study aims to investigate the effect of let-7a expression on survival outcomes of epithelial ovarian cancer (EOC) patients treated with different chemotherapy.Methods<br/>Let-7a expression was measured with qRT-PCR in ovarian tumors of 178 EOC patients who received platinum-based chemotherapy with and without paclitaxel after surgery. Survival analysis was performed to assess the effects of let-7a and chemotherapy on disease outcomes.Results<br/>Let-7a expression was detectable in the EOC samples, but the expression was not associated with disease stage, tumor grade, histology and debulking results. Patients who responded to platinum with paclitaxel had significantly lower let-7a than those who did not. Survival analyses showed that patients with high let-7a had better survival compared to those with low let-7a when they were treated with platinum without paclitaxel. The hazards ratios (HRs) for death and disease progression were 0.52 (95% CI: 0.29-0.96) and 0.48 (0.26-0.89) for high let-7a when compared to low let-7a, respectively. However, when patients were treated with platinum and paclitaxel, high let-7a was associated with worse progression-free and overall survival. The HRs for death and disease progression were 3.87 (95% CI: 1.28-11.66) and 3.48 (95% CI: 1.25-9.67) for high let-7a when compared to low let-7a, respectively. Further studies showed that among patients with low let-7a, those treated with paclitaxel in addition to platinum survived better than those treated without paclitaxel [adjusted-HRs were 0.31 (95% CI: 0.15-0.66) for death and 0.40 (95% CI: 0.22-0.75) for disease], while among those with high let-7a, the two types of treatment made no difference in patient survival.Conclusions<br/>The study suggests that the beneficial impact of the addition of paclitaxel on EOC survival was significantly linked to let-7a levels, and that miRNAs such as let-7a may be a useful marker for selection of chemotherapeutic agents in EOC management.</p>",
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            "creatorSummary": "Chan et al.",
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            "title": "MicroRNA signatures differentiate melanoma subtypes",
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                    "firstName": "Elcie",
                    "lastName": "Chan"
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                {
                    "creatorType": "author",
                    "firstName": "Rajeshvari",
                    "lastName": "Patel"
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                    "firstName": "Elena",
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                    "creatorType": "author",
                    "firstName": "Kathleen",
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                    "firstName": "Sebastian",
                    "lastName": "Szpakowski"
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                    "firstName": "Sirie",
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                    "creatorType": "author",
                    "firstName": "Stephan",
                    "lastName": "Ariyan"
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                    "creatorType": "author",
                    "firstName": "Mario",
                    "lastName": "Sznol"
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                    "creatorType": "author",
                    "firstName": "Ruth",
                    "lastName": "Halaban"
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                    "creatorType": "author",
                    "firstName": "Michael",
                    "lastName": "Krauthammer"
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                {
                    "creatorType": "author",
                    "firstName": "David",
                    "lastName": "Tuck"
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                {
                    "creatorType": "author",
                    "firstName": "Frank J",
                    "lastName": "Slack"
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                    "creatorType": "author",
                    "firstName": "Joanne Barnes",
                    "lastName": "Weidhaas"
                }
            ],
            "abstractNote": "Melanoma is an aggressive cancer that is highly resistance to therapies once metastasized. We studied microRNA (miRNA) expression in clinical melanoma subtypes and evaluated different miRNA signatures in the background of gain of function somatic and inherited mutations associated with melanoma. Total RNA from 42 patient derived primary melanoma cell lines and three independent normal primary melanocyte cell cultures was evaluated by miRNA array. MiRNA expression was then analyzed comparing subtypes and additional clinicopathologic criteria including somatic mutations. The prevalence and association of an inherited variant in a miRNA binding site in the 3'UTR of the KRAS oncogene, referred to as the KRAS-variant, was also evaluated. We show that seven miRNAs, miR-142-3p, miR-486, miR-214, miR-218, miR-362, miR-650 and miR-31, were significantly correlated with acral as compared to non-acral melanomas (p < 0.04). In addition, we discovered that the KRAS-variant was enriched in non-acral melanoma (25%), and that miR-137 under expression was significantly associated with melanomas with the KRAS-variant. Our findings indicate that miRNAs are differentially expressed in melanoma subtypes and that their misregulation can be impacted by inherited gene variants, supporting the hypothesis that miRNA misregulation reflects biological differences in melanoma.",
            "publicationTitle": "Cell Cycle (Georgetown, Tex.)",
            "publisher": "",
            "place": "",
            "date": "Jun 1, 2011",
            "volume": "10",
            "issue": "11",
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            "pages": "",
            "series": "",
            "seriesTitle": "",
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            "journalAbbreviation": "Cell Cycle",
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            "url": "http://www.ncbi.nlm.nih.gov/pubmed/21543894",
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            "rights": "",
            "extra": "PMID: 21543894",
            "tags": [
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                    "tag": "classification"
                },
                {
                    "tag": "melanoma"
                },
                {
                    "tag": "mirna"
                },
                {
                    "tag": "toget"
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            ],
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    {
        "key": "SKNUQZFK",
        "version": 1,
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            "type": "group",
            "id": 46360,
            "name": "cancer miRNA",
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            },
            "creatorSummary": "Ellwanger et al.",
            "parsedDate": "2011-05-15",
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        "data": {
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            "version": 1,
            "itemType": "journalArticle",
            "title": "The sufficient minimal set of miRNA seed types",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "Daniel C.",
                    "lastName": "Ellwanger"
                },
                {
                    "creatorType": "author",
                    "firstName": "Florian A.",
                    "lastName": "Büttner"
                },
                {
                    "creatorType": "author",
                    "firstName": "Hans-Werner",
                    "lastName": "Mewes"
                },
                {
                    "creatorType": "author",
                    "firstName": "Volker",
                    "lastName": "Stümpflen"
                }
            ],
            "abstractNote": "Motivation: Pairing between the target sequence and the 6–8 nt long seed sequence of the miRNA presents the most important feature for miRNA target site prediction. Novel high-throughput technologies such as Argonaute HITS-CLIP afford meanwhile a detailed study of miRNA:mRNA duplices. These interaction maps enable a first discrimination between functional and non-functional target sites in a bulky fashion. Prediction algorithms apply different seed paradigms to identify miRNA target sites. Therefore, a quantitative assessment of miRNA target site prediction is of major interest.Results: We identified a set of canonical seed types based on a transcriptome wide analysis of experimentally verified functional target sites. We confirmed the specificity of long seeds but we found that the majority of functional target sites are formed by less specific seeds of only 6 nt indicating a crucial role of this type. A substantial fraction of genuine target sites arenon-conserved. Moreover, the majority of functional sites remain uncovered by common prediction methods.Contact: florian.buettner@helmholtz-muenchen.de v.stuempflen@helmholtz-muenchen.deSupplementary Information: Supplementary data are available at Bioinformatics online.",
            "publicationTitle": "Bioinformatics",
            "publisher": "",
            "place": "",
            "date": "May 15 , 2011",
            "volume": "27",
            "issue": "10",
            "section": "",
            "partNumber": "",
            "partTitle": "",
            "pages": "1346 -1350",
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            "journalAbbreviation": "",
            "DOI": "10.1093/bioinformatics/btr149",
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            "url": "http://bioinformatics.oxfordjournals.org/content/27/10/1346.abstract",
            "accessDate": "2011-05-24T21:10:19Z",
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            "tags": [
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                    "tag": "mirna"
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                {
                    "tag": "target-prediction"
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                    "tag": "toread"
                }
            ],
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            "dateAdded": "2011-05-26T16:00:20Z",
            "dateModified": "2011-05-26T16:00:20Z"
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    },
    {
        "key": "HVU99ZJU",
        "version": 1,
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            "id": 46360,
            "name": "cancer miRNA",
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            },
            "creatorSummary": "Plaisier et al.",
            "parsedDate": "2011-05-20",
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        },
        "data": {
            "key": "HVU99ZJU",
            "version": 1,
            "itemType": "journalArticle",
            "title": "miRvestigator: web application to identify miRNAs responsible for co-regulated gene expression patterns discovered through transcriptome profiling",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "Christopher L",
                    "lastName": "Plaisier"
                },
                {
                    "creatorType": "author",
                    "firstName": "J Christopher",
                    "lastName": "Bare"
                },
                {
                    "creatorType": "author",
                    "firstName": "Nitin S",
                    "lastName": "Baliga"
                }
            ],
            "abstractNote": "Transcriptome profiling studies have produced staggering numbers of gene co-expression signatures for a variety of biological systems. A significant fraction of these signatures will be partially or fully explained by miRNA-mediated targeted transcript degradation. miRvestigator takes as input lists of co-expressed genes from Caenorhabditis elegans, Drosophila melanogaster, G. gallus, Homo sapiens, Mus musculus or Rattus norvegicus and identifies the specific miRNAs that are likely to bind to 3' un-translated region (UTR) sequences to mediate the observed co-regulation. The novelty of our approach is the miRvestigator hidden Markov model (HMM) algorithm which systematically computes a similarity P-value for each unique miRNA seed sequence from the miRNA database miRBase to an overrepresented sequence motif identified within the 3'-UTR of the query genes. We have made this miRNA discovery tool accessible to the community by integrating our HMM algorithm with a proven algorithm for de novo discovery of miRNA seed sequences and wrapping these algorithms into a user-friendly interface. Additionally, the miRvestigator web server also produces a list of putative miRNA binding sites within 3'-UTRs of the query transcripts to facilitate the design of validation experiments. The miRvestigator is freely available at http://mirvestigator.systemsbiology.net.",
            "publicationTitle": "Nucleic Acids Research",
            "publisher": "",
            "place": "",
            "date": "May 20, 2011",
            "volume": "",
            "issue": "",
            "section": "",
            "partNumber": "",
            "partTitle": "",
            "pages": "",
            "series": "",
            "seriesTitle": "",
            "seriesText": "",
            "journalAbbreviation": "Nucleic Acids Res",
            "DOI": "10.1093/nar/gkr374",
            "citationKey": "",
            "url": "http://www.ncbi.nlm.nih.gov/pubmed/21602264",
            "accessDate": "2011-05-24T21:38:28Z",
            "PMID": "",
            "PMCID": "",
            "ISSN": "1362-4962",
            "archive": "",
            "archiveLocation": "",
            "shortTitle": "miRvestigator",
            "language": "",
            "libraryCatalog": "NCBI PubMed",
            "callNumber": "",
            "rights": "",
            "extra": "PMID: 21602264",
            "tags": [
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            ],
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            "dateAdded": "2011-05-26T16:00:06Z",
            "dateModified": "2011-05-26T16:00:06Z"
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