دورية أكاديمية
MiR-17-92 fine-tunes MYC expression and function to ensure optimal B cell lymphoma growth
| العنوان: | MiR-17-92 fine-tunes MYC expression and function to ensure optimal B cell lymphoma growth |
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| المؤلفون: | M. Mihailovich, M. Bremang, V. Spadotto, D. Musiani, E. Vitale, G. Varano, F. M. Mancuso, D. A. Cairns, S. Casola, T. Bonaldi, F. Zambelli, G. Pavesi |
| المساهمون: | M. Mihailovich, M. Bremang, V. Spadotto, D. Musiani, E. Vitale, G. Varano, F. Zambelli, F.M. Mancuso, D.A. Cairn, G. Pavesi, S. Casola, T. Bonaldi |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2015 |
| المجموعة: | The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| مصطلحات موضوعية: | Animal, Cell Line, Tumor, Checkpoint Kinase 2, Cloning, Molecular, ELAV-Like Protein 1, Gene Expression Regulation, Neoplastic, Lymphoma, B-Cell, Mice, Transgenic, MicroRNA, Proteome, Proto-Oncogene Proteins c-myc, Biochemistry, Genetics and Molecular Biology (all), Chemistry (all), Physics and Astronomy (all), Settore BIO/11 - Biologia Molecolare |
| الوصف: | The synergism between c-MYC and miR-17-19b, a truncated version of the miR-17-92 cluster, is well-documented during tumor initiation. However, little is known about miR-17-19b function in established cancers. Here we investigate the role of miR-17-19b in c-MYC-driven lymphomas by integrating SILAC-based quantitative proteomics, transcriptomics and 3′ untranslated region (UTR) analysis upon miR-17-19b overexpression. We identify over one hundred miR-17-19b targets, of which 40% are co-regulated by c-MYC. Downregulation of a new miR-17/20 target, checkpoint kinase 2 (Chek2), increases the recruitment of HuR to c-MYC transcripts, resulting in the inhibition of c-MYC translation and thus interfering with in vivo tumor growth. Hence, in established lymphomas, miR-17-19b fine-tunes c-MYC activity through a tight control of its function and expression, ultimately ensuring cancer cell homeostasis. Our data highlight the plasticity of miRNA function, reflecting changes in the mRNA landscape and 3' UTR shortening at different stages of tumorigenesis. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/26555894; info:eu-repo/semantics/altIdentifier/wos/WOS:000366290600002; volume:6; firstpage:1; lastpage:15; numberofpages:15; journal:NATURE COMMUNICATIONS; http://hdl.handle.net/2434/458023Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84946910965 |
| DOI: | 10.1038/ncomms9725 |
| الإتاحة: | https://doi.org/10.1038/ncomms9725Test http://hdl.handle.net/2434/458023Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.284873CD |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/ncomms9725 |
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