Table 1.
Experimentally verified cooperative miRNAs
| Target gene | Cooperating miRNAs | Reagents | Effect | Phenotype | Cancer | Reference |
|---|---|---|---|---|---|---|
| CCNE1 and other genes | miR-34a, miR-15/16 | Precursor | Synergistic | Cell cycle arrest | NSCLC (in vitro) | (33) |
| APOE, DNAJA4 | miR-1908, miR-199a, miR-199a | Inhibitors | Synergistic | Metastasis | Melanoma (in vitro, in vivo) | (34) |
| Multiple genes | miR-125b, miR-100, miR-99a | Precursor | Synergistic | Chemoresistance | ALL (in vitro) | (35) |
| n/a | miR-20a, miR-21 | Inhibitors | Synergistic | Apoptosis | Glioma (in vitro) | (36) |
| PDCD4, BTG2*, NEDD4L | miR-21, miR-23a, miR-27a | Inhibitors | Synergistic | Tumor growth | PDAC (in vitro, in vivo) | (37) |
| E2F1* | miR-205, miR-342 | Mimics | Synergistic | Chemoresistance | Melanoma NSCLC (in vitro) | (41) |
| CDKN1A* | miR-572, miR-93 | Mimics | Synergistic | n/a | Melanoma (in vitro) | (49) |
| TGFBR2 | miR-9, miR-130b | Mimics | Additive | n/a | NSCLC (in vitro) | (50) |
| DMPK* | miR-206, miR-148a | Precursor | Synergistic | n/a | n/a | (51) |
| RASA1, SPRED1 | miR-21, miR-206 | Mimics | Synergistic | Apoptosis | TNBC (in vitro) | (52) |
| RUNX3 | miR-130a, miR-495 | Mimics, inhibitors | Synergistic | Apoptosis Angiogenesis | GC (in vitro, in vivo) | (53) |
| PDCD4, TPM1, RhoC, HoxD10, EGFR, MMP2 | miR-21, miR-10b | Inhibitors | Synergistic | Chemoresistance Tumor proliferation and invasion | Glioma (in vitro, in vivo) | (40,100) |
The table lists experimentally verified cooperative miRNAs that regulate the expression of a gene or a phenotype in a concerted manner. The genes with adjacent (13–35 nts) miRNA binding sites are highlighted by asterisks. The regulatory effect is derived from a quantitative analysis of gene or phenotype regulation by the specified miRNAs. The effect is additive when any amount of one miRNA can be substituted with the same amount of the other miRNA without increasing or decreasing the effect of the treatment; the effect is synergistic when the combined treatment leads to a significantly stronger effect than a treatment with the same total amount of either miRNA. The effects of gene regulation by cooperative miRNAs on cell phenotypes are also given if confirmed in the study, and the category of the experiments (in vitro or in vivo) is specified. Non-small cell lung cancer (NSCLC); acute lymphoblastic leukemia (ALL); pancreatic ductal adenocarcinoma (PDAC); triple-negative breast cancer (TNBC); gastric cancer (GC); not available (n/a)