miR-19, a component of the oncogenic miR-17∼92 cluster, targets the DNA-end resection factor CtIP
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
MicroRNA-19 (miR-19) was recently identified as the key oncogenic component of the polycistronic miR-17∼92 cluster, also known as oncomiR-1, which is frequently upregulated or amplified in multiple tumor types. However, the gene targets and the pathways underlying the tumor-promoting activity of miR-19 still remain largely elusive. CtIP/RBBP8 promotes DNA-end resection, a critical step in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR), and is considered to function as a tumor suppressor. In this study, we show that miR-19 downregulates CtIP expression by binding to two highly conserved sequences located in the 3'-untranslated region of CtIP mRNA. We further demonstrate that CtIP expression is repressed by miR-19 during continuous genotoxic stress in a p53-dependent manner. Finally, we report that miR-19 impairs CtIP-mediated DNA-end resection, which results in reduced HR levels and DNA damage hypersensitivity. By downregulating CtIP, miR-19 overexpression suppresses the faithful repair of DSBs that is crucial for genome maintenance. Our findings thus provide new mechanistic insight into the oncogenic role of the miR-17∼92 cluster.Oncogene advance online publication, 13 October 2014; doi:10.1038/onc.2014.329.
Originalsprog | Engelsk |
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Tidsskrift | Oncogene |
Vol/bind | 0 |
Sider (fra-til) | 3977-3984 |
Antal sider | 8 |
ISSN | 0950-9232 |
DOI | |
Status | Udgivet - 2015 |
ID: 138141004