Sistema de Salut de Catalunya
Institut Català de la Salut
[Segura MF] Department of Pathology, New York University School of Medicine, New York, NY, USA. Interdisciplinary Melanoma Cooperative Group, New York University Perlmutter Cancer Institute, NYU School of Medicine, New York, NY, USA. Grup Recerca translacional amb càncer infantil, Vall d'Hebron Institut de Rercerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Jubierre L, Soriano A, Masanas M] Grup Recerca translacional amb càncer infantil, Vall d'Hebron Institut de Rercerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Li S] Departments of Structural and Chemical Biology, Genetics and Genomic Sciences and Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA. [Koetz L, Gaziel-Sovran A] Department of Pathology, New York University School of Medicine, New York, NY, USA. Interdisciplinary Melanoma Cooperative Group, New York University Perlmutter Cancer Institute, NYU School of Medicine, New York, NY, USA
Vall d'Hebron Barcelona Hospital Campus
2021-04-27T09:53:12Z
2021-04-27T09:53:12Z
2017-04-18
Cèl·lules mare embrionàries; Melanoma; MicroARN
Células madre embrionarias; Melanoma; MicroARN
Embryonic stem cells; Melanoma; MicroRNA
MicroRNAs (miRNAs) are a class of endogenous non-coding small RNAs that post-transcriptionally control the translation and stability of target mRNAs in a sequence-dependent manner. MiRNAs are essential for key cellular processes including proliferation, differentiation, cell death and metabolism, among others. Consequently, alterations of miRNA expression contribute to developmental defects and a myriad of diseases. The expression of miRNAs can be altered by several mechanisms including gene copy number alterations, aberrant DNA methylation, defects of the miRNA processing machinery or unscheduled expression of transcription factors. In this work, we sought to analyze the regulation of the miR-182 cluster, located at the 7q32 locus, which encodes three different miRNAs that are abundantly expressed in human embryonic stem cells and de-regulated in cancer. We have found that the Krüppel-like factor 4 (KLF4) directly regulates miR-182 cluster expression in human embryonic stem cells (hESCs) and in melanoma tumors, in which the miR-182 cluster is highly expressed and has a pro-metastatic role. Furthermore, higher KLF4 expression was found to be associated with metastatic progression and poor patient outcome. Loss of function experiments revealed that KLF4 is required for melanoma cell maintenance. These findings provide new insights into the regulation of the miR-182 cluster expression and new opportunities for therapeutic intervention in tumors in which the KLF4-miR-182 cluster axis is deregulated.
This work was supported by NCI/NIH Grant (5R01CA155234), Instituto de Salud Carlos III (CP11/00052 and RD12/0036/0016) co-financed by the European Regional Development Fund (ERDF), and European Commission’s Framework Programme 7 through the Marie Curie Career Integration Grants.
Article
Published version
English
Tumors; Cèl·lules mare embrionàries; Factors de transcripció; ANATOMY::Cells::Stem Cells::Pluripotent Stem Cells::Embryonic Stem Cells::Human Embryonic Stem Cells; DISEASES::Neoplasms; CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Kruppel-Like Transcription Factors; ANATOMÍA::células::células madre::células madre pluripotentes::células madre embrionarias::células madre embrionarias humanas; ENFERMEDADES::neoplasias; COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas de unión al ADN::factores de transcripción similares a Kruppel
Impact Journals
Oncotarget;8(16)
https://www.oncotarget.com/article/15459/text/
info:eu-repo/grantAgreement/ES/1PN/2008-2011/CP11%2F00052
info:eu-repo/grantAgreement/ES/2PN/2008-2011/RD12%2F0036%2F0016
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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