Using microRNA array technology, they found that 4-AP altered the miRNAs expression in glioma cells, and the down-regulation of miR-10b-5p induced by 4-AP was verified by real-time PCR. Transfection of miR-10b-5p mimic significantly inhibited 4-AP-induced caspases activation and apoptosis. Moreover, they verified that apoptosis-related molecule Apaf-1 was the direct target of miR-10b-5p. Furthermore, miR-10b-5p mimic significantly inhibited 4-AP-induced up-regulation of Apaf-1 and its downstream apoptosis-related proteins, such as cleaved caspase-3.
In conclusion, Kv channel blocker 4-AP may exert its antitumor effect by down-regulating the expression of miR-10b-5p, and then raising expression of Apaf-1 and its downstream apoptosis-related proteins. These current data provide evidence that miRNAs play important roles in Kv channel-mediated cell proliferation and apoptosis.