Fig. 1

Schematic mechanism of p53-miRNA interaction in MM. TS-miRs known to be regulated by wtp53 (e.g., miR-192) target negative regulators of wtp53 like MDM2 and gankyrin or target cell cycle-related/anti-apoptotic proteins to enhance tumor suppressor activity of wtp53. However, this scenario is compromised in MM context possibly due to epigenetic silencing of TS-miRs or wtp53 and also due to upregulation of negative regulators. Therefore, the outcome will be a suppressed wtp53 which ends in downregulation of p53 downstream targets such as PUMA, BAX, and NOXA, maintenance of MM cells survival, and probably resistance to anti-myeloma drugs. On the other hand, oncomiRs (e.g., miR-125b) negatively regulate p53 either by directly targeting p53 or by targeting positive regulators of p53 (such as PCAF) which culminates in the same outcomes as above. Of note, wtp53 can also regulate miRNA biogenesis by association with DROSHA or DICER, a function which is completely antagonized by mtp53. In MM, mtp53 may function as an oncogene by interfering with biogenesis of TS-miRs which could partly explain the resistance of mtp53 phenotypes to anti-myeloma drugs (however, this concept demands in-depth investigation in MM)