Cargando…

Voltage-gated potassium channel blocker 4-aminopyridine induces glioma cell apoptosis by reducing expression of microRNA-10b-5p

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 apoptos...

Descripción completa

Detalles Bibliográficos
Autores principales: Ru, Qin, Li, Wei-ling, Xiong, Qi, Chen, Lin, Tian, Xiang, Li, Chao-Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921578/
https://www.ncbi.nlm.nih.gov/pubmed/29514931
http://dx.doi.org/10.1091/mbc.E17-02-0120
_version_ 1783318043645968384
author Ru, Qin
Li, Wei-ling
Xiong, Qi
Chen, Lin
Tian, Xiang
Li, Chao-Ying
author_facet Ru, Qin
Li, Wei-ling
Xiong, Qi
Chen, Lin
Tian, Xiang
Li, Chao-Ying
author_sort Ru, Qin
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5921578
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher The American Society for Cell Biology
record_format MEDLINE/PubMed
spelling pubmed-59215782018-07-16 Voltage-gated potassium channel blocker 4-aminopyridine induces glioma cell apoptosis by reducing expression of microRNA-10b-5p Ru, Qin Li, Wei-ling Xiong, Qi Chen, Lin Tian, Xiang Li, Chao-Ying Mol Biol Cell Articles 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. The American Society for Cell Biology 2018-05-01 /pmc/articles/PMC5921578/ /pubmed/29514931 http://dx.doi.org/10.1091/mbc.E17-02-0120 Text en © 2018 Ru et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0/ This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Articles
Ru, Qin
Li, Wei-ling
Xiong, Qi
Chen, Lin
Tian, Xiang
Li, Chao-Ying
Voltage-gated potassium channel blocker 4-aminopyridine induces glioma cell apoptosis by reducing expression of microRNA-10b-5p
title Voltage-gated potassium channel blocker 4-aminopyridine induces glioma cell apoptosis by reducing expression of microRNA-10b-5p
title_full Voltage-gated potassium channel blocker 4-aminopyridine induces glioma cell apoptosis by reducing expression of microRNA-10b-5p
title_fullStr Voltage-gated potassium channel blocker 4-aminopyridine induces glioma cell apoptosis by reducing expression of microRNA-10b-5p
title_full_unstemmed Voltage-gated potassium channel blocker 4-aminopyridine induces glioma cell apoptosis by reducing expression of microRNA-10b-5p
title_short Voltage-gated potassium channel blocker 4-aminopyridine induces glioma cell apoptosis by reducing expression of microRNA-10b-5p
title_sort voltage-gated potassium channel blocker 4-aminopyridine induces glioma cell apoptosis by reducing expression of microrna-10b-5p
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921578/
https://www.ncbi.nlm.nih.gov/pubmed/29514931
http://dx.doi.org/10.1091/mbc.E17-02-0120
work_keys_str_mv AT ruqin voltagegatedpotassiumchannelblocker4aminopyridineinducesgliomacellapoptosisbyreducingexpressionofmicrorna10b5p
AT liweiling voltagegatedpotassiumchannelblocker4aminopyridineinducesgliomacellapoptosisbyreducingexpressionofmicrorna10b5p
AT xiongqi voltagegatedpotassiumchannelblocker4aminopyridineinducesgliomacellapoptosisbyreducingexpressionofmicrorna10b5p
AT chenlin voltagegatedpotassiumchannelblocker4aminopyridineinducesgliomacellapoptosisbyreducingexpressionofmicrorna10b5p
AT tianxiang voltagegatedpotassiumchannelblocker4aminopyridineinducesgliomacellapoptosisbyreducingexpressionofmicrorna10b5p
AT lichaoying voltagegatedpotassiumchannelblocker4aminopyridineinducesgliomacellapoptosisbyreducingexpressionofmicrorna10b5p