E2F1-Regulated MicroRNAs Impair TGFβ-Dependent Cell-Cycle Arrest and Apoptosis in Gastric Cancer

Fabio Petrocca, 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

Research output: Contribution to journalArticle

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Abstract

Deregulation of E2F1 activity and resistance to TGFβ 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 TGFβ tumor suppressor pathway, interfering with the expression of CDKN1A (p21Waf1/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 TGFβ resistance in gastric cancer.

Original languageEnglish
Pages (from-to)272-286
Number of pages15
JournalCancer Cell
Volume13
Issue number3
DOIs
Publication statusPublished - Mar 11 2008

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Cell Cycle Checkpoints
MicroRNAs
Stomach Neoplasms
Apoptosis
Small Untranslated RNA
Neoplasms
Stomach
Up-Regulation
Genes

Keywords

  • CELLBIO

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Petrocca, F., Visone, R., Onelli, M. R., Shah, M. H., Nicoloso, M. S., de Martino, I., ... Vecchione, A. (2008). E2F1-Regulated MicroRNAs Impair TGFβ-Dependent Cell-Cycle Arrest and Apoptosis in Gastric Cancer. Cancer Cell, 13(3), 272-286. https://doi.org/10.1016/j.ccr.2008.02.013

E2F1-Regulated MicroRNAs Impair TGFβ-Dependent Cell-Cycle Arrest and Apoptosis in Gastric Cancer. / Petrocca, Fabio; Visone, Rosa; Onelli, Mariadele Rapazzotti; Shah, Manisha H.; Nicoloso, Milena S.; de Martino, Ivana; Iliopoulos, Dimitrios; Pilozzi, Emanuela; Liu, Chang Gong; Negrini, Massimo; Cavazzini, Luigi; Volinia, Stefano; Alder, Hansjuerg; Ruco, Luigi P.; Baldassarre, Gustavo; Croce, Carlo M.; Vecchione, Andrea.

In: Cancer Cell, Vol. 13, No. 3, 11.03.2008, p. 272-286.

Research output: Contribution to journalArticle

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 2008, 'E2F1-Regulated MicroRNAs Impair TGFβ-Dependent Cell-Cycle Arrest and Apoptosis in Gastric Cancer', Cancer Cell, vol. 13, no. 3, pp. 272-286. https://doi.org/10.1016/j.ccr.2008.02.013
Petrocca F, Visone R, Onelli MR, Shah MH, Nicoloso MS, de Martino I et al. E2F1-Regulated MicroRNAs Impair TGFβ-Dependent Cell-Cycle Arrest and Apoptosis in Gastric Cancer. Cancer Cell. 2008 Mar 11;13(3):272-286. https://doi.org/10.1016/j.ccr.2008.02.013
Petrocca, Fabio ; Visone, Rosa ; Onelli, Mariadele Rapazzotti ; Shah, Manisha H. ; Nicoloso, Milena S. ; de Martino, Ivana ; Iliopoulos, Dimitrios ; Pilozzi, Emanuela ; Liu, Chang Gong ; Negrini, Massimo ; Cavazzini, Luigi ; Volinia, Stefano ; Alder, Hansjuerg ; Ruco, Luigi P. ; Baldassarre, Gustavo ; Croce, Carlo M. ; Vecchione, Andrea. / E2F1-Regulated MicroRNAs Impair TGFβ-Dependent Cell-Cycle Arrest and Apoptosis in Gastric Cancer. In: Cancer Cell. 2008 ; Vol. 13, No. 3. pp. 272-286.
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