Role of Yin Yang-1 (YY1) in the transcription regulation of the multi-drug resistance ( <i>MDR1</i> ) gene

Abstract

Resistance to chemotherapy hinders the successful treatment of acute lymphoblastic leukemia (ALL). The multi-drug resistance-1 (<i>MDR1</i>/ABCB1) gene encodes P-glycoprotein (P-gp), which plays an important role in chemoresistance; however, its transcriptional regulation remains unclear. We investigated the role of YY1 in the regulation of <i>MDR1</i> and its relation to ALL outcomes. Analysis of the <i>MDR1</i> promoter revealed four putative YY1-binding sites, which we analyzed using a reporter system and ChIP analysis. YY1 silencing resulted in the inhibition of <i>MDR1</i> expression and function. The clinical roles of YY1 and <i>MDR1</i> expression were evaluated in children with ALL. Expression of both proteins was increased in ALL patients compared to controls. We identified a positive correlation between YY1 and <i>MDR1</i> expression. High levels of YY1 were associated with decreased overall survival. Our results demonstrated that YY1 regulates the transcription of <i>MDR1</i>. Therefore, YY1 may serve as a useful prognostic and/or therapeutic target.