title: miR-1228 promotes the proliferation and metastasis of hepatoma cells through a p53 forward feedback loop.
abstract: BACKGROUND
  The effective mechanisms of microRNAs (miRNAs) functions as oncogenes or tumour suppressors in human hepatocellular carcinoma (HCC) are still obscure. Here, we investigated the function and expression of miR-1228 in HCC.
  
  
  METHODS
  The role of miR-1228 in HCC was determined by colony formation, transwell, and nude mice xenograft experiments. miR-1228 target gene were identified by EGFP reporter assays, real-time PCR, and western blot analysis. Dual-luciferase reporter assay and real-time PCR analysis are used to examine the regulation of p53.
  
  
  RESULTS
  miR-1228 promoted proliferation and metastasis, and facilitated the transition of cell cycle in hepatoma cells. miR-1228 downregulated p53 expression by binding to its 3'UTR. The ectopic expression of p53 abrogated the phenotypes induced by miR-1228. An inverse correlation existed between miR-1228 and p53 expression in hepatoma tissues compared with the adjacent tissues and three hepatoma cell lines. Moreover, we found that p53 suppressed the expression and promoter activity of miR-1228.
  
  
  CONCLUSIONS
  miR-1228 functions as an oncogene by promoting cell cycle progression and cell mobility and negatively regulates the expression of p53. p53 downregulation in turn leads to an increase in miR-1228 expression, thereby forming a positive feedback loop that contributes to cancerogenesis in HCC.
authors.affiliation: Tianjin Life Science Research Center, Department of Microbiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 30070, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Tianjin Life Science Research Center, Department of Microbiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 30070, China.
authors.forename: J
authors.initials: J
authors.lastname: Dai
authors.affiliation: Tianjin Life Science Research Center, Department of Microbiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 30070, China.
authors.forename: H
authors.initials: H
authors.lastname: Deng
authors.affiliation: Tianjin Life Science Research Center, Department of Microbiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 30070, China.
authors.forename: H
authors.initials: H
authors.lastname: Wan
authors.affiliation: Tianjin Life Science Research Center, Department of Microbiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 30070, China.
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oncology in Southern China, Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncology in Southern China, Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.affiliation: Tianjin Life Science Research Center, Department of Microbiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 30070, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Tianjin Life Science Research Center, Department of Microbiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 30070, China.
authors.forename: H
authors.initials: H
authors.lastname: Tang
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D002465:Cell Movement; D049109:Cell Proliferation; D025461:Feedback, Physiological; D059585:G1 Phase Cell Cycle Checkpoints; D059565:G2 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: C576906:MIRN1228 microRNA, human; D035683:MicroRNAs; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53