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Yin Yang 1 overexpression in diffuse large B-cell lymphoma is associated with B-cell transformation and tumor progression

Giancarlo Castellano, Elena Torrisi, Giovanni Ligresti, Ferdinando Nicoletti, Grazia Malaponte, Salvatore Travali, James A. McCubrey, Silvana Canevari and Massimo Libra

Yin Yang 1 (YY1), a multifunctional transcription factor, has been shown to be involved in the pathogenesis of several cancer types. However, its role in hematological malignancies has not yet been fully investigated. In the present study, using computational methods, we showed that YY1 transcript levels were significantly increased in the high-grade lymphomas, including Burkitt’s lymphoma and diffuse large B-cell lymphoma (DLBCL), compared with those of both low-grade lymphomas and normal B-cells. The significant increase in gene expression resulted in a significant increase also at protein level in three NHL cell lines. The association of YY1 expression with some clinical-pathological features in DLBCL showed a positive correlation between a high level of YY1 mRNA and high levels of BCL-6 protein. Moreover, by analyzing the large series of DLBCL in the Hummel dataset, we identified the transcription factor PAX-5 among the top 50 genes positively correlated with YY1. These findings are also supported by the biological network analysis in which the top network, with the highest score, associated with YY1 expression levels in DLBCL is cellular movement, hematological system development and function, and immune response. Overall these data suggest that YY1 is involved in B cells transformation which gives rise to high-grade lymphomas through a dysregulation in the normal development of B cells affecting cell cycle and cellular motility.

Authors

Giancarlo Castellano

Istituto Nazionale dei Tumori; Milan, Italy

Elena Torrisi

University of Catania; Catania, Italy

Giovanni Ligresti

University of Catania; Catania, Italy

Ferdinando Nicoletti

University of Catania; Catania, Italy

Grazia Malaponte

University of Catania; Catania, Italy

Salvatore Travali

University of Catania; Catania, Italy

James A. McCubrey

East Carolina University; Greenville, NC

Silvana Canevari

Istituto Nazionale dei Tumori; Milan, Italy

Massimo Libra Corresponding author: mlibra@unict.it

University of Catania; Catania, Italy