Differentiation-associated microRNAs antagonize the Rb-E2F pathway to restrict proliferation

Matteo J. Marzi, Eleonora M R Puggioni, Valentina Dall'Olio, Gabriele Bucci, Loris Bernard, Fabrizio Bianchi, Marco Crescenzi, Pier Paolo Di Fiore, Francesco Nicassio

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The cancer-associated loss of microRNA (miRNA) expression leads to a proliferative advantage and aggressive behavior through largely unknown mechanisms. Here, we exploit a model system that recapitulates physiological terminal differentiation and its reversal upon oncogene expression to analyze coordinated mRNA/miRNA responses. The cell cycle reentry of myotubes, forced by the E1A oncogene, was associated with a pattern of mRNA/miRNA modulation that was largely reciprocal to that induced during the differentiation of myoblasts into myotubes. The E1A-induced mRNA response was preponderantly Retinoblastoma protein (Rb)-dependent. Conversely, the miRNA response was mostly Rb-independent and exerted through tissue-specific factors and Myc. A subset of these miRNAs (miR-1, miR-34, miR-22, miR-365, miR-29, miR-145, and Let-7) was shown to coordinately target Rb-dependent cell cycle and DNA replication mRNAs. Thus, a dual level of regulation-transcriptional regulation via Rb-E2F and posttranscriptional regulation via miRNAs-confers robustness to cell cycle control and provides a molecular basis to understand the role of miRNA subversion in cancer.

Original languageEnglish
Pages (from-to)77-95
Number of pages19
JournalJournal of Cell Biology
Volume199
Issue number1
DOIs
Publication statusPublished - Oct 1 2012

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MicroRNAs
Messenger RNA
Skeletal Muscle Fibers
Oncogenes
Cell Cycle
Retinoblastoma Protein
Myoblasts
Thromboplastin
Cell Cycle Checkpoints
DNA Replication
Neoplasms

ASJC Scopus subject areas

  • Cell Biology

Cite this

Differentiation-associated microRNAs antagonize the Rb-E2F pathway to restrict proliferation. / Marzi, Matteo J.; Puggioni, Eleonora M R; Dall'Olio, Valentina; Bucci, Gabriele; Bernard, Loris; Bianchi, Fabrizio; Crescenzi, Marco; Di Fiore, Pier Paolo; Nicassio, Francesco.

In: Journal of Cell Biology, Vol. 199, No. 1, 01.10.2012, p. 77-95.

Research output: Contribution to journalArticle

Marzi, Matteo J. ; Puggioni, Eleonora M R ; Dall'Olio, Valentina ; Bucci, Gabriele ; Bernard, Loris ; Bianchi, Fabrizio ; Crescenzi, Marco ; Di Fiore, Pier Paolo ; Nicassio, Francesco. / Differentiation-associated microRNAs antagonize the Rb-E2F pathway to restrict proliferation. In: Journal of Cell Biology. 2012 ; Vol. 199, No. 1. pp. 77-95.
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