Wilms’ tumor gene 1 silencing inhibits proliferation of human osteosarcoma MG-63 cell line by cell cycle arrest and apoptosis activation

Adriana Carol Eleonora Graziano; Venera Cardile; Rosanna Avola; Nunzio Vicario; Carmela Parenti; Lucia Salvatorelli; Gaetano Magro; Rosalba Parenti

doi:10.18632/oncotarget.14715

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Research Papers:

Wilms’ tumor gene 1 silencing inhibits proliferation of human osteosarcoma MG-63 cell line by cell cycle arrest and apoptosis activation

Adriana Carol Eleonora Graziano, Venera Cardile, Rosanna Avola, Nunzio Vicario, Carmela Parenti, Lucia Salvatorelli, Gaetano Magro and Rosalba Parenti _

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Oncotarget. 2017; 8:13917-13931. https://doi.org/10.18632/oncotarget.14715

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Abstract

Adriana Carol Eleonora Graziano1, Venera Cardile1, Rosanna Avola1, Nunzio Vicario1, Carmela Parenti2, Lucia Salvatorelli3, Gaetano Magro3, Rosalba Parenti1

1Department of Biomedical and Biotechnological Sciences, Physiology Section, University of Catania, 95125 Catania, Italy

2Department of Drug Sciences, Pharmacology and Toxicology Section, University of Catania, 95125 Catania, Italy

3Department G.F. Ingrassia, Azienda Ospedaliero-Universitaria ‘‘Policlinico-Vittorio Emanuele’’ Anatomic Pathology, University of Catania, 95125 Catania, Italy

Correspondence to:

Rosalba Parenti, email: [email protected]

Keywords: WT1, apoptosis, osteosarcoma, oncogene, cell cycle

Received: August 08, 2016 Accepted: January 06, 2017 Published: January 18, 2017

ABSTRACT

Wilms’ tumor gene 1 (WT1) plays complex roles in tumorigenesis, acting as tumor suppressor gene or an oncogene depending on the cellular context. A high WT1 expression level was described in various types of human bone and soft-tissue sarcomas, including osteosarcoma (OS), but its function in carcinogenesis is not yet well understood. This study investigated WT1 both in human OS tissues and in human OS MG-63 cell line in which WT1 gene is up-regulated. The results demonstrated that WT1 is expressed in 50% of human OS cases. WT1-silenced MG-63 cells showed deregulation of proteins of cell cycle and down-regulation of PI3K/AKT pathway. Induction of apoptotic programme was also established by activation of caspase-3 and increase of Bax/Bcl2 ratio and p53 protein. This study provided new findings on role of WT1 and indicated an association between WT1 expression, cell cycle and apoptotic machinery. In conclusion, WT1 acts as a tumour promoter in osteosarcoma and it could be a potential therapeutic target.

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Research Papers:

Wilms’ tumor gene 1 silencing inhibits proliferation of human osteosarcoma MG-63 cell line by cell cycle arrest and apoptosis activation

Abstract