| Literature DB >> 18328430 |
Fabio Petrocca1, Rosa Visone, Mariadele Rapazzotti Onelli, Manisha H Shah, Milena S Nicoloso, Ivana de Martino, Dimitrios Iliopoulos, Emanuela Pilozzi, Chang-Gong Liu, Massimo Negrini, Luigi Cavazzini, Stefano Volinia, Hansjuerg Alder, Luigi P Ruco, Gustavo Baldassarre, Carlo M Croce, Andrea Vecchione.
Abstract
Deregulation of E2F1 activity and resistance to TGFbeta are hallmarks of gastric cancer. MicroRNAs (miRNAs) are small noncoding RNAs frequently misregulated in human malignancies. Here we provide evidence that the miR-106b-25 cluster, upregulated in a subset of human gastric tumors, is activated by E2F1 in parallel with its host gene, Mcm7. In turn, miR-106b and miR-93 regulate E2F1 expression, establishing a miRNA-directed negative feedback loop. Furthermore, upregulation of these miRNAs impairs the TGFbeta tumor suppressor pathway, interfering with the expression of CDKN1A (p21(Waf1/Cip1)) and BCL2L11 (Bim). Together, these results suggest that the miR-106b-25 cluster is involved in E2F1 posttranscriptional regulation and may play a key role in the development of TGFbeta resistance in gastric cancer.Entities:
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Year: 2008 PMID： 18328430 DOI： 10.1016/j.ccr.2008.02.013
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743