Poster abstracts

Poster number 66 submitted by Sung-Suk Suh

Down-regulation of p53-inducible microRNAs 92,94 and 215 impairs the p53/MDM2 auto-regulatory loop in multiple myeloma development

Sung-Suk Suh (MVIMG), Flavia Pichiorri (MVIMG), Alberto Rocci (MVIMG), Luciana De Luca (MVIMG)

Abstract:
In multiple myeloma (MM), an incurable B-cell neoplasm, mutation or deletion of p53 is rarely detected at diagnosis. Mechanisms that maintain p53 inactivity in early stage MM are not fully understood. Using small-molecule inhibitors of MDM2, we discovered a mechanism of p53 activation through MDM2 down regulation by miR-192, 194 and 215, which themselves can be transcriptionally activated by p53. We observed that these miRNAs are severely reduced in many untreated MM samples compared with Monoclonal Gammopathy of Undetermined Significance (MGUS) and normal plasma cells, in which MDM2 is significantly up-regulated. The data provide evidence of novel functional links between these miRNAs and p53, underscoring a critical role for these pathways in MM progression.

Keywords: miRNA, TP53, MDM2