Table 1.
Pharmacological strategies to modulate the LIN28/let-7 axis.
| Strategy | Selected Agent | Mechanism of Action | Cellular Effect | Reference |
|---|---|---|---|---|
| Let-7 mimics | Let-7i mimic | Restoration of let-7i level | Inhibition of the growth and migration of lung cancer cells | [74] |
| Let-7a mimic | Restoration of let-7a level | Suppression of Wnt signaling in esophageal squamous cell carcinoma (ESCC) cells | [75] | |
| Looptomirs | L29-13 | Antagonization of LIN28A docking at pre-let-7a-2 | Restoration of let-7 synthesis and inhibition of growth and clonogenic potential in hepatocarcinomatous cells overexpressing LIN28B | [76] |
| Small-molecule inhibitors | Compound 1 | Prevention of LIN28A binding to pre-let-7a-1 through unknown molecular mechanism | Enhancement of let-7 production in LIN28-expressing cancer cells (LIN28A and LIN28B) | [83] |
| 6-hydroxy-DL-DOPA | Prevention of LIN28A binding to pre-let-7g through unknown molecular mechanism | N/A | [87] | |
| SB/ZW/0065 | Prevention of LIN28A binding to pre-let-7g through unknown molecular mechanism | N/A | [87] | |
| Compound 1632 | Prevention of LIN28B binding to pre-let-7a-2 through unknown molecular mechanism | Reduction in let-7 level and tumor sphere formation in LIN28-expressing cancer cells; induction of mouse embryonic stem cell differentiation | [88] | |
| TPEN | Chelation of LIN28A ZKD-bound Zn2+ and destabilization of LIN28A ZKD | N/A | [86] | |
| LI71 | Competition for the pre-let-7f-1 interaction site of LIN28A CSD | Suppression of LIN28 activity and restoration of mature let-7 level in leukemia cells (LIN28B) and embryonic stem cells (LIN28A) | [86] | |
| Gossypol (LI11) | Prevention of LIN28A binding to pre-let-7f-1 through unknown molecular mechanism | N/A | [86] | |
| MNA (LI101) | Putatively by competition for the pre-let-7f-1 interaction site of LIN28A CSD | Suppression of LIN28 function in HeLa cells expressing LIN28A or LIN28B | [86] | |
| Trisubstituted pyrrolinones (C902) | Putatively by competition for the pre-let-7f-1 interaction site of LIN28A CSD | Increase in mature let-7 levels in human choriocarcinoma cell line JAR cells | [81] | |
| Compound 4j (GG-43) | Prevention of LIN28 binding to pre-let-7 through unknown molecular mechanism | Compound 4j barely showed any inhibitory activity in human choriocarcinoma cell line JAR cells | [82] |