Accumulating evidence has demonstrated that voltage-gated potassium channels (Kv channels) are associated with regulating cell proliferation and apoptosis in tumor cells. A previous study proved that Kv channel blocker, 4-aminopyridine (4-AP) could inhibit cell proliferation and induce apoptosis in glioma. However, the precise mechanisms were not clear yet. Because small non-coding RNAs act as key mediators in the progression of tumors, researchers at Jianghan University sought to investigate the role of miRNAs in the apoptosis-promoting effect of 4-AP in glioma cells.

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.

 

Reference
Q. Ru, WL Li, Q. Xiong, L. Chen, X. Tian, CY Li (2018) Voltage-gated potassium channel blocker 4-aminopyridine induces glioma cell apoptosis by reducing expression of microRNA-10b-5p Molecular Biology of the Cell doi: 10.1091/mbc.E17-02-0120 [abstract]

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