title: Voltage‑gated K+ channel blocker quinidine inhibits proliferation and induces apoptosis by regulating expression of microRNAs in human glioma U87‑MG cells.
abstract: Accumulating evidence has proved that potassium channels (K+ channels) are involved in regulating cell proliferation, cell cycle progression and apoptosis of tumor cells. However, the precise cellular mechanisms are still unknown. In the present study, we investigated the effect and mechanisms of quinidine, a commonly used voltage-gated K+ channel blocker, on cell proliferation and apoptosis of human glioma U87-MG cells. We found that quinidine significantly inhibited the proliferation of U87-MG cells and induced apoptosis in a dose-dependent manner. The results of caspase colorimetric assay showed that the mitochondrial pathway was the main mode involved in the quinidine-induced apoptotic process. Furthermore, the concentration range of quinidine, which inhibited voltage-gated K+ channel currents in electrophysiological assay, was consistent with that of quinidine inhibiting cell proliferation and inducing cell apoptosis. In U87-MG cells treated with quinidine (100 µmol/l), 11 of 2,042 human microRNAs (miRNAs) were upregulated and 16 were downregulated as detected with the miRNA array analysis. The upregulation of miR-149-3p and downregulation of miR-424-5p by quinidine treatment were further verified by using quantitative real-time PCR. In addition, using miRNA target prediction program, putative target genes related to cell proliferation and apoptosis for two differentially expressed miRNAs were predicted. Taken together, these data suggested that the anti-proliferative and pro-apoptosis effect of voltage-gated K+ channel blocker quinidine in human glioma cells was mediated at least partly through regulating expression of miRNAs, and provided further support for the mechanisms of voltage-gated K+ channels in mediating cell proliferation and apoptosis.
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan, Hubei 430056, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Ru
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan, Hubei 430056, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Tian
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan, Hubei 430056, P.R. China.
authors.forename: Ming-Shan
authors.initials: MS
authors.lastname: Pi
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan, Hubei 430056, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan, Hubei 430056, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Yue
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan, Hubei 430056, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xiong
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan, Hubei 430056, P.R. China.
authors.forename: Bao-Miao
authors.initials: BM
authors.lastname: Ma
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan, Hubei 430056, P.R. China.
authors.forename: Chao-Ying
authors.initials: CY
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D026902:Potassium Channel Blockers / Q000008:administration & dosage; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors / Q000378:metabolism; D011802:Quinidine / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D035683:MicroRNAs; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D011802:Quinidine