title: Tumor-suppressing effect of miR-4458 on human hepatocellular carcinoma.
abstract: BACKGROUND
  Besides multiple genetic and epigenetic changes of protein coding genes in hepatocellular carcinoma (HCC), growing evidence indicate that deregulation of miRNAs contribute to HCC development by influencing cell growth, apoptosis, migration, or invasion. IKBKE is amplified and over-expressed in a large percentage of human breast tumors and identified as an oncogene of human breast tumor. Microarray analysis showed that miR-4458 was down-regulated in HCC tissues.
  
  
  METHODS
  The level of miR-4458 was up-regulated by miR-4458 mimics transfection, or down-regulated by miR-4458 ASO transfection. Cell proliferation was assayed by MTT analysis. MiRNAs and mRNA expression were assayed by qRT-PCR. These potential targeted genes of miR-4458 were predicted by bioinformatic algorithms. Dual luciferase reporter assay system was used to analyze the interaction between miR-4458 and IKBKE. IKBKE protein level was assayed by Western blot. The role of miR-4458 or IKBKE in the survival of HCC patients were revealed by Kaplan-Meier plot of overall survival.
  
  
  RESULTS
  Lower miR-4458 expression level or higher IKBKE level in HCC tissues correlated with worse prognosis of HCC patients. Overexpression of miR-4458 inhibited the HCC cells growth and vice versa. MiR-4458 played its role via targeting 3'UTR of IKBKE.
  
  
  CONCLUSIONS
  MiR-4458 or IKBKE may be potential predictors of HCC prognosis. Restoration of miR-4458 or inhibition of IKBKE could be a prospective therapeutic approach for HCC.
authors.affiliation: Department of Gastroenterology, Chinese PLA 89 Hospital, Weifang, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Tang
authors.forename: Baomu
authors.initials: B
authors.lastname: Sun
authors.forename: Hongyu
authors.initials: H
authors.lastname: Yu
authors.forename: Zhengde
authors.initials: Z
authors.lastname: Yang
authors.forename: Liang
authors.initials: L
authors.lastname: Zhu
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056945:Hep G2 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D011379:Prognosis; D016415:Sequence Alignment
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D051550:I-kappa B Kinase; C496565:IKBKE protein, human