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

被引：880

作者：

Petrocca, Fabio ^{[1
,5
,6
]}

Visone, Rosa ^{[1
]}

Onelli, Mariadele Rapazzotti ^{[3
]}

Shah, Manisha H. ^{[2
]}

Nicoloso, Milena S. ^{[1
,4
]}

de Martino, Ivana ^{[1
]}

Iliopoulos, Dimitrios ^{[1
]}

Pilozzi, Emanuela ^{[3
]}

Liu, Chang-Gong ^{[1
]}

Negrini, Massimo ^{[5
,6
]}

Cavazzini, Luigi ^{[5
,6
]}

Volinia, Stefano ^{[1
,5
,6
]}

Alder, Hansjuerg ^{[1
]}

Ruco, Luigi P. ^{[2
]}

Baldassarre, Gustavo ^{[4
]}

Croce, Carlo M. ^{[1
]}

Vecchione, Andrea ^{[1
,3
]}

机构：

[1] Ohio State Univ, Human Canc Genet Program, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA

[2] Ohio State Univ, Ctr Comprehens Canc, Div Hematol & Oncol, Columbus, OH 43210 USA

[3] Univ Rome La Sapienza 2, Osped Santo Andrea, Div Pathol, I-00189 Rome, Italy

[4] IRCCS, CRO, Div Expt Oncol 2, I-33081 Aviano, Italy

[5] Univ Ferrara, Dept Expt & Diagnost Med, Telethon Facil Data Min Anal DNA Microarrays, I-44100 Ferrara, Italy

[6] Univ Ferrara, Dept Oncol, I-44100 Ferrara, Italy

来源：

CANCER CELL | 2008年 / 13卷 / 03期

关键词：

D O I：

10.1016/j.ccr.2008.02.013

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：272 / 286

页数：15

共 48 条

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