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

Abstract

Resistance to chemotherapy hinders the successful treatment of acute lymphoblastic leukemia (ALL). The multi-drug resistance-1 (MDR1/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 MDR1 and its relation to ALL outcomes. Analysis of the MDR1 promoter revealed four putative YY1-binding sites, which we analyzed using a reporter system and ChIP analysis. YY1 silencing resulted in the inhibition of MDR1 expression and function. The clinical roles of YY1 and MDR1 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 MDR1 expression. High levels of YY1 were associated with decreased overall survival. Our results demonstrated that YY1 regulates the transcription of MDR1. Therefore, YY1 may serve as a useful prognostic and/or therapeutic target.

Keywords:

• Acute lymphoblastic leukemia
• MDR1
• YY1
• children
• chemoresistance

Acknowledgements

The authors would like to thank the National Council of Science and Technology, the Mexico Federal Funds of Hospital Infantil de Mexico Federico Gomez, the Mexican Foundation of Health and Merck, and El Patronato del Hospital Infantil de México.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2018.1448083.

Additional information

Funding

The study was funded by the National Council of Science and Technology [2007-C01-69789 CONACYT, S.H.-Y], the Mexico Federal Funds [Grant HIM/2011/009, S.H.-Y., G.A-A.], and the Mexican Foundation of Health and Merck [Grant F769, S.H.-Y].