E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer.

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.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Petrocca F,Visone R,Onelli MR,Shah MH,Nicoloso MS,de Martino I,Iliopoulos D,Pilozzi E,Liu CG,Negrini M,Cavazzini L,Volinia S,Alder H,Ruco LP,Baldassarre G,Croce CM,Vecchione A

doi

10.1016/j.ccr.2008.02.013

subject

Has Abstract

pub_date

2008-03-01 00:00:00

pages

272-86

issue

3

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(08)00049-4

journal_volume

13

pub_type

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