Deregulated miRNAs in Hereditary Breast Cancer Revealed a Role for miR-30c in Regulating KRAS Oncogene

作者: Miljana Tanic , Kira Yanowsky , Cristina Rodriguez-Antona , Raquel Andrés , Iván Márquez-Rodas

DOI: 10.1371/JOURNAL.PONE.0038847

关键词: ErbBTumor progressionKRASBreast cancerGene expression profilingCancer researchmicroRNAOncogeneBiologyMicroarray analysis techniques

摘要: Aberrant miRNA expression has been previously established in breast cancer and clinical relevance. However, no studies so far have defined miRNAs deregulated hereditary tumors. In this study we investigated the role of tumors comparing with normal tissue. Global profiling using Exiqon microarrays was performed on 22 15 non-tumoral tissues. We identified 19 differentially expressed, most them down-regulated An important proportion were commonly sporadic Under-expression these validated by qRT-PCR additional 18 their tissue counterparts. Pathway enrichment analysis revealed that collectively targeted a number genes belonging to signaling pathways such as MAPK, ErbB, mTOR, those regulating cell motility or adhesion. silico prediction detected KRAS oncogene target several miRNAs. particular, experimentally miR-30c target. Luciferase assays confirmed binds 3′UTR transcripts pre-miR-30c mRNA protein. Furthermore, overexpression inhibited proliferation cells. Our results identify associated cancer, well miss-expressed tumors, suggesting common underlying mechanisms tumor progression. addition, provide evidence is miR-30c, suppresses growth potentially through inhibition signaling.

参考文章(38)
J Palacios, MJ Robles Frías, MA Castilla, MA Lopez-Garcia, J Benitez, The molecular pathology of hereditary breast cancer. Pathobiology. ,vol. 75, pp. 85- 94 ,(2008) , 10.1159/000123846
Geoffrey J. Clark, Channing J. Der, Aberrant function of the Ras signal transduction pathway in human breast cancer Breast Cancer Research and Treatment. ,vol. 35, pp. 133- 144 ,(1995) , 10.1007/BF00694753
Charles M. Perou, Therese Sørlie, Michael B. Eisen, Matt van de Rijn, Stefanie S. Jeffrey, Christian A. Rees, Jonathan R. Pollack, Douglas T. Ross, Hilde Johnsen, Lars A. Akslen, Øystein Fluge, Alexander Pergamenschikov, Cheryl Williams, Shirley X. Zhu, Per E. Lønning, Anne-Lise Børresen-Dale, Patrick O. Brown, David Botstein, Molecular portraits of human breast tumours Nature. ,vol. 406, pp. 747- 752 ,(2000) , 10.1038/35021093
E. R. Morrissey, R. Diaz-Uriarte, Pomelo II: finding differentially expressed genes. Nucleic Acids Research. ,vol. 37, pp. 581- 586 ,(2009) , 10.1093/NAR/GKP366
Shuangni Yu, Zhaohui Lu, Changzheng Liu, Yunxiao Meng, Yihui Ma, Wugan Zhao, Jianping Liu, Jia Yu, Jie Chen, miRNA-96 Suppresses KRAS and Functions as a Tumor Suppressor Gene in Pancreatic Cancer Cancer Research. ,vol. 70, pp. 6015- 6025 ,(2010) , 10.1158/0008-5472.CAN-09-4531
Lin He, Gregory J. Hannon, MicroRNAs: small RNAs with a big role in gene regulation Nature Reviews Genetics. ,vol. 5, pp. 522- 531 ,(2004) , 10.1038/NRG1379
Katherine L Dunn, Paula S Espino, Bojan Drobic, Shihua He, James R Davie, The Ras-MAPK signal transduction pathway, cancer and chromatin remodeling Biochemistry and Cell Biology. ,vol. 83, pp. 1- 14 ,(2005) , 10.1139/O04-121
Blenkiron C Goldstein LD Thorne NP, Spiteri I Chin SF, None, MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype Genome Biology. ,vol. 8, pp. 1- 16 ,(2007) , 10.1186/GB-2007-8-10-R214
Stefano Volinia, George A. Calin, Chang-Gong Liu, Stefan Ambs, Amelia Cimmino, Fabio Petrocca, Rosa Visone, Marilena Iorio, Claudia Roldo, Manuela Ferracin, Robyn L. Prueitt, Nozumu Yanaihara, Giovanni Lanza, Aldo Scarpa, Andrea Vecchione, Massimo Negrini, Curtis C. Harris, Carlo M. Croce, A microRNA expression signature of human solid tumors defines cancer gene targets Proceedings of the National Academy of Sciences of the United States of America. ,vol. 103, pp. 2257- 2261 ,(2006) , 10.1073/PNAS.0510565103
Marilena V. Iorio, Manuela Ferracin, Chang-Gong Liu, Angelo Veronese, Riccardo Spizzo, Silvia Sabbioni, Eros Magri, Massimo Pedriali, Muller Fabbri, Manuela Campiglio, Sylvie Ménard, Juan P. Palazzo, Anne Rosenberg, Piero Musiani, Stefano Volinia, Italo Nenci, George A. Calin, Patrizia Querzoli, Massimo Negrini, Carlo M. Croce, MicroRNA gene expression deregulation in human breast cancer. Cancer Research. ,vol. 65, pp. 7065- 7070 ,(2005) , 10.1158/0008-5472.CAN-05-1783