Role of the transcription factor yy1 in b cell non-hodgkin lymphoma development

• Main Authors: S. Vivarelli, L. Falzone, M. Libra
• Format: Article
• Language: English
• Published: PAGEPress Publications 2020-09-01
• Series: Hematology Reports
• Online Access: https://www.pagepress.org/journals/index.php/hr/article/view/8928

Introduction Yin Yang 1 (YY1) is a transcription factor with a dual role in cancer. B-cell non-Hodgkin lymphomas (B-NHLs) are often characterized by the development of recurrence and/or resistance to therapy. The aim of this study was to investigate the pro-tumorigenic function of YY1 in reversing drug-resistance, as well as to identify YY1 downstream resistant factors in B-NHLs. Methods Predictive studies coupled with analyses of deposited-Chip-Sequencing, as well as Gene Expression Omnibus (GEO) B-NHL repositories, were used to: (1) Identify YY1 transcriptional target(s) which may regulate the apoptosis; (2) Assess the diagnostic role of YY1 and the identified target(s). The in-silico studies were subsequently validated in vitro by using a model of aggressive Burkitt’s Lymphoma (BL), the Raji cell line. Results The bioinformatics analyses suggested that: (1) YY1 bound the promoter of the BIRC5/survivin anti-apoptotic gene; (2) Both YY1 and survivin were highly expressed in B-NHLs, especially in aggressive ones; (3) There was a conserved positive correlation between YY1 and survivin in all the B-NHL GEO datasets analyzed. Validation experiments performed in Raji cells further demonstrated that YY1 silencing: (1) was associated with survivin downregulation; (2) sensitized the cells to apoptosis. Conclusions Overall, our results revealed that: (1) Survivin could be proposed as YY1 transcriptional target; (2) YY1 and survivin are positively correlated and both found overexpressed in B-NHLs, especially in BLs; (3) YY1 knockdown sensitizes Raji cells to drug-induced apoptosis via downregulation of survivin; (4) both YY1 and survivin might be suggested as potential diagnostic biomarkers and therapeutic targets for the treatment of resistant/recurrent B-NHLs.