Table 1 miRNAs which function as negative or positive regulators of wtp53
From: Role of tumor suppressor p53 and micro-RNA interplay in multiple myeloma pathogenesis
miRNA | Expression pattern | P53 status of the HMCLs used | Functional responses and targets | Refs. |
|---|---|---|---|---|
miR-125b | Upregulation (UR) | Wild type (wt) | MM cells overexpressed miR-125b when exposed to DEX leading to reduced apoptosis by targeting p53. miR-34a which targeted SIRT1 was also induced by DEX, thus maintained deacetylation and inactivation of p53. Inhibition of miR-125b enhanced p53 expression, suppressed SIRT1, and increased DEX-induced apoptosis | [20] |
miR-125a | UR | wt | miR-125a-5p mimics downregulated the expression of TP53, BAX, MDM2, CDKN1A, and GADD45. p53 was directly targeted by miR-125a-5p. Moreover, inhibition of miR-125a-5p dampened cell growth, increased apoptosis, and reduced cell migration | [21] |
miR-34a | Downregulation (DR) | wt and mutant (MT) | Synthetic miR-34a downregulated canonic targets BCL2, CDK6, and NOTCH1 at both the mRNA and protein level. In a xenograft model of mtp53, miR-34a mimics also reduced tumor growth | [27] |
miR-34a | DR | wt and MT | Overexpression of miR-34a reduced the level of Bcl-2, CDK4, CDK6, CEBPα, and YY, sensitized them to BTZ, and reduced tumor growth in vivo | [29] |
miR-214 | DR | wt | miR-214 overexpression in H929 cells resulted in suppression of PSMD10 and ASF1B. Inhibition of gankyrin increased P53 mRNA levels and subsequently upregulated CDKN1A (p21Waf1/Cip1) and BAX transcripts, which are direct transcriptional targets of p53 | [32] |
miR-192/194/212 | DR | wt and MT | MDM2 inhibitor nutlin-3a upregulated p53 and 3 p53-inducible miRNAs, miR-192/194/215. Ectopic expression of these miRNAs in wtp53 HMCLs upregulated CDKN1A but not in mtp53 lines. Furthermore, while wtp53 HMCLs were sensitive to miRNA upregulation, mtp53 cells showed some level of resistance | [38] |
miR-25 and miR-30d | UR | wt | Inhibition of miR-25 or miR-30d increased the endogenous protein levels of p53, Bax, p21, and PUMA and induced apoptosis, while ectopic overexpression of these miRNAs decreased p53, p21, and GADD45 and reduced apoptosis and cell cycle arrest. p53, p21, and Bax were decreased even in the presence of the genotoxic agent etoposide | [39] |
miR-106b~25 cluster, miR-32, miR-181a/b | UR | wt | These miRNAs targeted p300-CBP-associated factor (PCAF), an activator of wtp53. Inhibition of all these miRNAs highly upregulated TP53 following exposure to UV light | [54] |