Authors: Irene Marchesi, Francesco Paolo Fiorentino, Flavio Rizzolio, Antonio Giordano and Luigi Bagella

Irene Marchesi

Department of Biomedical Sciences; Division of Biochemistry and National Institute of Biostructures and Biosystems; University of Sassari; Sassari, Italy; Sbarro Institute for Cancer Research and Molecular Medicine; Center for Biotechnology; College of Science and Technology; Temple University; Philadelphia, PA USA

Francesco Paolo Fiorentino

Sbarro Institute for Cancer Research and Molecular Medicine; Center for Biotechnology; College of Science and Technology; Temple University; Philadelphia, PA USA

Flavio Rizzolio

Sbarro Institute for Cancer Research and Molecular Medicine; Center for Biotechnology; College of Science and Technology; Temple University; Philadelphia, PA USA

Antonio Giordano

Sbarro Institute for Cancer Research and Molecular Medicine; Center for Biotechnology; College of Science and Technology; Temple University; Philadelphia, PA USA; Human Pathology and Oncology Department; University of Siena; Siena, Italy

Luigi Bagella

Corresponding author: lbagella@uniss.it
Department of Biomedical Sciences; Division of Biochemistry and National Institute of Biostructures and Biosystems; University of Sassari; Sassari, Italy; Sbarro Institute for Cancer Research and Molecular Medicine; Center for Biotechnology; College of Science and Technology; Temple University; Philadelphia, PA USA

Abstract:
Rhabdomyosarcoma (RMS) is a pediatric tumor that arises from muscle precursor cells. RMS cells express several markers of early myogenic differentiation, but they fail to complete both differentiation program and cell cycle arrest, resulting in uncontrolled proliferation and incomplete myogenesis. Previous studies showed that EZH2, which is involved in both differentiation and cancer progression, is overexpressed in RMS, but a functional binding between its expression and its functional role in tumor formation or progression has not yet been demonstrated. We hypothesized that EZH2 is a key regulator of muscular differentiation program in RMS cells.

In this study, we demonstrated that EZH2 directly binds muscle specific genes in RD cells. Silencing of EZH2 promotes the recruitment of a multiprotein complex at muscle-specific promoters, their transcriptional activation and protein expression. Moreover, we demonstrated that EZH2 is directly involved in transcriptional repression of MyoD, the main factor promoting myogenesis. EZH2 ablation induces MyoD activation the recovery of its binding on muscle-specific genes.

Received: March 13, 2012; Accepted: August 30, 2012; Published Online: September 14, 2012

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