title: Roles of microRNA-330 and Its Target Gene ING4 in the Development of Aggressive Phenotype in Hepatocellular Carcinoma Cells.
abstract: Aberrant expression of microRNAs contributes to tumor growth and progression.
  
  
  
  This study was designed to explore the prognostic and biological significance of miR-330 in hepatocellular carcinoma (HCC).
  
  
  
  The expression of miR-330 and its associations with tumor parameters and overall survival were analyzed in HCC patients. The biological functions of miR-330 in HCC cell growth, invasion, and tumorigenesis were investigated. Bioinformatic analysis and luciferase reporter assays were performed to search for potential targets of miR-330.
  
  
  
  The miR-330 level was significantly higher in HCCs than in adjacent normal tissues (P = 0.0085). High expression of miR-330 was significantly associated with more aggressive phenotypes and shorter overall survival in HCC. Loss- and gain-of-function studies indicated the favorable effect of miR-330 on tumor cell growth, invasion, and tumorigenesis. Inhibitor of growth 4 (ING4) was identified to be a direct target of miR-330. Overexpression of miR-330 reduced the expression of ING4 in HCC cells. Importantly, restoration of ING4 almost completely reversed the promotion of HCC cell proliferation and invasion by miR-330.
  
  
  
  Altogether, this study demonstrates that upregulation of miR-330 is associated with poor prognosis and contributes to more aggressive phenotypes of HCC. The oncogenic role of miR-330 in HCC is linked to downregulation of ING4.
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao, 266003, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao, 266003, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of ICU, The Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao, 266003, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Qu
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao, 266003, China. sunchuandong@hotmail.com.
authors.forename: Chuandong
authors.initials: C
authors.lastname: Sun
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002681:China / Q000453:epidemiology; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; C483230:ING4 protein, human; C570805:MIRN330 microRNA, human; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins
keywords: Growth; Invasion; Oncogene; Prognosis; microRNA