| http://purl.uniprot.org/citations/26314219 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26314219 | http://www.w3.org/2000/01/rdf-schema#comment | "Accumulating evidence indicates that microRNAs (miRs) regulate cancer metastasis. We have shown that miR-182 drives sarcoma metastasis in vivo by coordinated regulation of multiple genes. Recently, we also demonstrated that in a subset of primary sarcomas that metastasize to the lung, miR-182 expression is elevated through binding of MyoD1 to the miR-182 promoter. However, it is not known if there are also transcription factors that inhibit miR-182 expression. Defining negative regulators of miR-182 expression may help explain why some sarcomas do not metastasize and may also identify pathways that can modulate miR-182 for therapeutic benefit. Here, we use an in silico screen, chromatin-immunoprecipitation, and luciferase reporter assays to discover that Kruppel like factor-3 (Klf-3) is a novel transcriptional repressor of miR-182. Knockdown of Klf-3 increases miR-182 expression, and stable overexpression of Klf-3, but not a DNA-binding mutant Klf-3, decreases miR-182 levels. Klf-3 expression is downregulated in both primary mouse and human metastatic sarcomas, and Klf-3 levels negatively correlate with miR-182 expression. Interestingly, Klf-3 also negatively regulates MyoD1, suggesting an alternative mechanism for Klf-3 to repress miR-182 expression in addition to direct binding of the miR-182 promoter. Using Methylation Specific PCR (MSP) and pyrosequencing assays, we found that Klf-3 is epigenetically silenced by DNA hypermethylation both in mouse and human sarcoma cells. Finally, we show the DNA methylation inhibitor 5'Azacytidine (Aza) restores Klf-3 expression while reducing miR-182 levels. Thus, our findings suggest that demethylating agents could potentially be used to modulate miR-182 levels as a therapeutic strategy."xsd:string |
| http://purl.uniprot.org/citations/26314219 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.canlet.2015.08.016"xsd:string |
| http://purl.uniprot.org/citations/26314219 | http://purl.uniprot.org/core/author | "Ma Y."xsd:string |
| http://purl.uniprot.org/citations/26314219 | http://purl.uniprot.org/core/author | "Huang Z."xsd:string |
| http://purl.uniprot.org/citations/26314219 | http://purl.uniprot.org/core/author | "Kirsch D.G."xsd:string |
| http://purl.uniprot.org/citations/26314219 | http://purl.uniprot.org/core/author | "Sachdeva M."xsd:string |
| http://purl.uniprot.org/citations/26314219 | http://purl.uniprot.org/core/author | "Grenier C."xsd:string |
| http://purl.uniprot.org/citations/26314219 | http://purl.uniprot.org/core/author | "Murphy S.K."xsd:string |
| http://purl.uniprot.org/citations/26314219 | http://purl.uniprot.org/core/author | "Lev D.C."xsd:string |
| http://purl.uniprot.org/citations/26314219 | http://purl.uniprot.org/core/author | "Dodd R.D."xsd:string |
| http://purl.uniprot.org/citations/26314219 | http://purl.uniprot.org/core/author | "Cardona D.M."xsd:string |
| http://purl.uniprot.org/citations/26314219 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/26314219 | http://purl.uniprot.org/core/name | "Cancer Lett"xsd:string |
| http://purl.uniprot.org/citations/26314219 | http://purl.uniprot.org/core/pages | "202-211"xsd:string |
| http://purl.uniprot.org/citations/26314219 | http://purl.uniprot.org/core/title | "Epigenetic silencing of Kruppel like factor-3 increases expression of pro-metastatic miR-182."xsd:string |
| http://purl.uniprot.org/citations/26314219 | http://purl.uniprot.org/core/volume | "369"xsd:string |
| http://purl.uniprot.org/citations/26314219 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/26314219 |
| http://purl.uniprot.org/citations/26314219 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/26314219 |
| http://purl.uniprot.org/uniprot/#_A0A0N4SVY1-mappedCitation-26314219 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26314219 |
| http://purl.uniprot.org/uniprot/#_Q0VDV7-mappedCitation-26314219 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26314219 |
| http://purl.uniprot.org/uniprot/#_A0A158SIS7-mappedCitation-26314219 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26314219 |
| http://purl.uniprot.org/uniprot/#_A0A5Q0MU23-mappedCitation-26314219 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26314219 |
| http://purl.uniprot.org/uniprot/#_A0A1W2P863-mappedCitation-26314219 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26314219 |
| http://purl.uniprot.org/uniprot/#_B2R8P9-mappedCitation-26314219 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26314219 |