Accumulating evidence has demonstrated that
voltage-gated potassium channels (Kv channels) were associated with regulating cell proliferation and apoptosis in
tumor cells. Our previous study proved that the Kv channel blocker
4-aminopyridine (4-AP) could inhibit cell proliferation and induce apoptosis in
glioma. However, the precise mechanisms were not clear yet.
MicroRNAs (
miRNAs) are small noncoding RNAs that act as key mediators in the progression of
tumor, so the aim of this study was to investigate the role of
miRNAs in the apoptosis-promoting effect of 4-AP in
glioma cells. Using a
microRNA array, we found that 4-AP altered the
miRNA 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, we 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 anti-
tumor effect by down-regulating the expression of miR-10b-5p and then raised expression of Apaf-1 and its downstream apoptosis-related
proteins. Current data provide evidence that
miRNAs play important roles in Kv channels-mediated cell proliferation and apoptosis.