title: MiR-296-3p regulates cell growth and multi-drug resistance of human glioblastoma by targeting ether-à-go-go (EAG1).
abstract: MicroRNAs (miRNAs) - short non-coding RNA molecules - post-transcriptionally regulate gene expressions and play crucial roles in diverse biological processes such as development, differentiation, apoptosis and proliferation. In order to investigate the possible role of miRNAs in the development of multi-drug resistance (MDR) in human glioblastoma, we first detected (by Western blotting, real-time polymerase chain reaction [RT-PCR] and immunohistochemistry) the expression of miR-296-3p and ether-à-go-go (EAG1 or KCNH1) in U251 cells, U251/imatinib mesylate (U251AR cells) and clinical specimens. The results showed that miR-296-3p was down-regulated in U251AR cells, concurrent with the up-regulation of EAG1 protein, compared with the parental U251 cell line. In vitro drug sensitivity assay demonstrated that over-expression of miR-296-3p sensitised glioblastoma (GBM) cells to anticancer drugs, whereas down-expression using antisense oligonucleotides conferred MDR. Ectopic expression of miR-296-3p reduced EAG1 expression and suppressed cell proliferation drug resistance, and the luciferase activity of an EAG1 3'-untranslated region-based reporter construct in U251AR cells, whereas EAG1 over-expression rescued the suppressive effect of miR-296-3p in U251AR cells. We also found that EAG1 was widely over-expressed and inversely correlated with miR-296-3p in clinical specimens. Taken together, our findings suggest that miR-296-3p may play a role of MDR in glioblastoma at least in part by targeting EAG1.
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Bai
authors.forename: Hongzhan
authors.initials: H
authors.lastname: Liao
authors.forename: Tianzhu
authors.initials: T
authors.lastname: Liu
authors.forename: Xiangping
authors.initials: X
authors.lastname: Zeng
authors.forename: Faman
authors.initials: F
authors.lastname: Xiao
authors.forename: Luqiao
authors.initials: L
authors.lastname: Luo
authors.forename: Hongbo
authors.initials: H
authors.lastname: Guo
authors.forename: Linlang
authors.initials: L
authors.lastname: Guo
mesh_terms: D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics* / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D009361:Neoplasm Invasiveness
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C549871:MIRN296 microRNA, human; D035683:MicroRNAs