Abstract

rDNA transcription is steadily dysregulated in multiple myeloma, through oncogenes and anti-tumor routes, and particularly by c-Myc. The main downstream goals of c-Myc involve ribosomal biogenesis to enhance the protein translation capacity necessary to support the growth and self-renewal programs of malignancy cells. In the research of therapeutics to improve cancer treatment, the last 10 years have shown a renewed interest in targeting ribosome biogenesis. In the present study, we have demonstrated promise for CX-5461 as a new therapeutic target in multiple myeloma. We report that CX-5461 irreversibly inhibits ribosomal RNA (rRNA) transcription by arresting RNA polymerase I (RPI/Pol1/PolR1) in a transcription initiation complex causing down regulation of 47S and inducing the ribosomal stress. We showed that CX-5461 upregulated p53 pathway, and down regulated c-Myc causing cell cycle arrest and cell death

Keywords: CX-5461; TP53; Multiple myeloma; Cell cycle; 47S