Table 1 Outcomes of miR-34a modulation in models bearing p53 mutation
From: Alternative mechanisms of miR-34a regulation in cancer
Cancer type | Target cells | Type of p53 defect | Type of miR-34a modulation | Outcome | Reference |
|---|---|---|---|---|---|
Glioblastoma | U251 | R273H | Introduction of miRNA mimic | Inhibition of cell growth, cell cycle arrest, induction of apoptosis, reduction of in vitro migration and invasion capabilities | |
Myeloid leukemia | SKMM1 | R248H | Introduction of synthetic miRNA oligos, stable overexpression | Growth inhibition | |
RPMI-8226 | E285K | Introduction of synthetic miRNA oligos; intratumoral injection of formulated miR-34a | Growth inhibition; anti-tumor effect | ||
OPM1 | 5 mutations in exons | Introduction of synthetic miRNA oligos | Growth inhibition | ||
KASUMI-1 | R248Q | Introduction of miRNA precursors | Reduction of PD-L1 expression | ||
Lung cancer | SBC-5 | R248L | Introduction of miRNA precursor | Inhibition of proliferation, sensitization to cisplatin-based therapy | |
H23 | M246I | Introduction of synthetic miRNA oligos | Potentiation of the effect of EGFR inhibition | ||
Calu-6 | R196Stop | Introduction of synthetic miRNA oligos | Potentiation of the effect of EGFR inhibition | ||
PC-9 | R248Q | Introduction of synthetic miRNA oligos | Restoration of sensitivity to gefitinib | ||
344SQ | R172HΔG | Liposomal in vivo delivery of mature miRNA | Downregulation of immune-suppressive PDL-1, prevention of immune evasion | ||
Breast cancer | MDA-MB-231 | R280K | Inducible overexpression | Inhibition of cell migration and invasion | |
BT-549 | R249S | Introduction of miRNA precursor | Inhibition of cell migration and invasion | ||
Ovarian cancer | SK-OV-3 | H179R | Introduction of miRNA mimic | Reduced proliferation, motility, and invasion, no induction of apoptosis | |
SK-OV-3 | H179R | Introduction of miRNA mimic | Restoration of epithelial phenotype, downregulation of Snail | ||
ES-2 | S241F | Introduction of miRNA mimic | Restoration of epithelial phenotype, downregulation of Snail | ||
Prostate cancer | DU145 | P223L V274F | Introduction of synthetic miRNA oligos | Inhibition of cell proliferation and clonal expansion | |
DU145 | P223L V274F | In vivo co-delivery of doxorubicin and miR-34a using polypeptide-based cationic micelles | Inhibition of xenograft growth, induction of apoptosis/necrosis in vitro | 112 | |
DU145 - taxane resistant | P223L V274F | Rubone-induced stabilization combined with paclitaxel | Decreased cell viability | 113 | |
Bladder cancer | 5637 | R280T | Introduction of miRNA precursor | Reduced clonogenic capacity, induction of senescence, sensitization to cisplatin | |
T24 | In-frame deletion of Y126 | Introduction of miRNA precursor | Reduced clonogenic capacity, induction of senescence, sensitization to cisplatin | ||
Colon cancer | SW480 | R273H P309S | Inducible overexpression | Cell cycle arrest, downregulation of cell cycle regulators | |
SW480 | R273H P309S | Inhibition by antagomir | Induction of EMT-driving transcription factor Snail | ||
SW480 | R273H P309S | Inducible overexpression of pri-miR-34a | Restoration of epithelial phenotype, downregulation of stemness markers | ||
SW480 | R273H P309S | Introduction of miRNA mimic; inducible overexpression | No change in p53 expression | ||
Liver cancer | HuH7 | Y220C | Systemic liposomal delivery in mice | Decreased orthotopic tumor mass | 114 |
