Journal
CANCER CELL
Volume 13, Issue 3, Pages 272-286Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2008.02.013
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Funding
- Telethon [GTF03012] Funding Source: Medline
- Associazione Italiana per la Ricerca sul Cancro Funding Source: Custom
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Deregulation of E2F1 activity and resistance to TGF beta 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 TGF beta 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 TGF beta resistance in gastric cancer.
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