title: miRNAs Regulate hERG.
abstract: The human ether-a-go-go-related gene (hERG) is the major molecular component of the rapidly activating delayed rectifier K+current (Ikr). Impairment of hERG function is believed to be a mechanism causing long-QT syndromes (LQTS). Growing evidences have shown that microRNAs (miRNAs) are involved in functional modulation of the hERG pathway. The purpose of this study was to screen and validate miRNAs that regulate the hERG pathway. The miRNAs identified in this study will provide new tools to assess the mechanism of LQTS.
  
  
  
  Six miRNAs were selected by algorithm predictions based on potential interaction with hERG. The effects of each miRNA on hERG were assessed by use of the Dual-Luciferase Reporter assay system, qRT-PCR, Western blotting, and confocal fluorescence microscopy. Furthermore, whole-cell patch clamp technique was used to validate the effect of miR-103a-1 on the electrophysiological characteristic of the Ikrof the hERG protein channel.
  
  
  
  miR-134, miR-103a-1, miR-143, and miR-3619 significantly downregulated luciferase activity (P < 0.05) in a reporter test system. These 4 miRNAs significantly suppressed expression of hERG mRNA and protein in U2OS cells (P < 0.05).Corresponding AMOs rescued expression of hERG mRNA and protein. Confocal microscopy showed that all 4 miRNAs reduced the expression of both immature and mature hERG protein. miR-103a-1 decreased the maximum current and tail current amplitudes of hERG channel.
  
  
  
  Expression and functions of hERG are regulated by specific miRNAs.
authors: Li Hui Li Hospital, Medical School of NingBo University, NingBo, China.
authors: Jiangfang
authors: J
authors: Lian
authors: Li Hui Li Hospital, Medical School of NingBo University, NingBo, China.
authors: Jian
authors: J
authors: Guo
authors: Li Hui Li Hospital, Medical School of NingBo University, NingBo, China.
authors: Xiaoyan
authors: X
authors: Huang
authors: Li Hui Li Hospital, Medical School of NingBo University, NingBo, China.
authors: X I
authors: XI
authors: Yang
authors: Li Hui Li Hospital, Medical School of NingBo University, NingBo, China.
authors: Guochang
authors: G
authors: Huang
authors: Li Hui Li Hospital, Medical School of NingBo University, NingBo, China.
authors: Haiyan
authors: H
authors: Mao
authors: Department of Surgery, University of Rochester Medical Center, Rochester, New York, USA.
authors: Huan Huan
authors: HH
authors: Sun
authors: Li Hui Li Hospital, Medical School of NingBo University, NingBo, China.
authors: Yanna
authors: Y
authors: Ba
authors: Li Hui Li Hospital, Medical School of NingBo University, NingBo, China.
authors: Jianqing
authors: J
authors: Zhou
mesh_terms: D045744:Cell Line, Tumor; D019295:Computational Biology; D030541:Databases, Genetic; D015536:Down-Regulation; D000072237:ERG1 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating; D008133:Long QT Syndrome / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008564:Membrane Potentials; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D000072237:ERG1 Potassium Channel; C000606913:KCNH2 protein, human; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: AMOs; hERG; long-QT sydrome; microRNA; rapidly activating delayed rectifier potassium current