Journal
ONCOGENE
Volume 33, Issue 30, Pages 4003-4015Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2013.398
Keywords
DICER1; miRNA; colon cancer; stemness; metastasis
Funding
- Spanish Ministry of Science and Innovation [SAF200801173, SAF2011-22803]
- European Research Council Advanced Grant EPINORC [268626]
- European Community's Seventh Framework Programme (FP7) [HEALTH-F2-2011-259015-COLTHERES, HEALTH-F5-2010-258236-SYSCOL]
- Cellex Foundation
- Botin Foundation
- Health and Science Departments of the Catalan Government (Generalitat de Catalunya)
- Spanish Ministry of Science and Innovation fellowship
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Disruption of microRNA (miRNA) expression patterns is now being recognized as a hallmark of human cancer. The causes of these altered profiles are diverse, and, among them, we found the existence of defects in the miRNA processing machinery. However, little is known about how these alterations affect the biology of the underlying tumors. Herein, we show that colorectal cancer cells with an impairment in DICER1, a major miRNA biogenesis gene, undergo enrichment of tumor stemness features and an epithelialto- mesenchymal transition. These phenotypes are associated with the downregulation of miRNAs, such as miR-34a, miR-126 and those of the miR-200 family, that target critical coding genes in these pathways. Most importantly, DICER1 impairment also induces the acquisition of a greater capacity for tumor initiation and metastasis, two properties associated with cancer stem cells.
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