title: microRNA expression alteration after arsenic trioxide treatment in HepG-2 cells.
abstract: OBJECTIVE
  More and more microRNA (miRNA) are found to be involved in tumor genesis and progress. Arsenic trioxide has been an effective chemotherapeutic drug in cancer therapy for many years. In this study, we aimed to find the miRNA involved in the mechanisms of arsenic trioxide treatment in cancer therapy.
  
  
  METHODS
  We detected the expression profile of miRNA by miRNA microarray and quantitative real-time polymerase chain reaction. Cell viability assay, flow cytometry analysis, prediction of miRNA targets, Western blot analysis and luciferase reporter assay were carried out to determine the role of one selected miRNA, namely mir-29a, in affecting the biological behaviors of HepG-2 cells.
  
  
  RESULTS
  Among the 677 human miRNA in the microarray, five miRNA were upregulated and four were downregulated in HepG-2 cells treated with arsenic trioxide compared to their controls. If only changes above two folds were considered, four miRNA were identified, namely miR-24, miR-29a, miR-30a and miR-210, which were all upregulated. Among them, miR-29a showed a positive therapeutic effect in liver cancer cells by inhibiting cell growth and inducing cell apoptosis, and PPM1D was confirmed to be the target gene of miR-29a. Furthermore, a synergy effect was detected between miR-29a and arsenic trioxide.
  
  
  CONCLUSIONS
  Arsenic trioxide altered miRNA expression profile in HepG-2 cells. Among the altered miRNA, miR-29a seemed to take a role in the mechanism of arsenic trioxide in liver cancer therapy. The synergy effect between miR-29a and arsenic trioxide may offer this drug a new chance in cancer therapy by decreasing its dose and toxic side-effects.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Xian-Zhi
authors.initials: XZ
authors.lastname: Meng
authors.forename: Tong-Sen
authors.initials: TS
authors.lastname: Zheng
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Jia-Bei
authors.initials: JB
authors.lastname: Wang
authors.forename: Wei-Hui
authors.initials: WH
authors.lastname: Zhang
authors.forename: Shang-Ha
authors.initials: SH
authors.lastname: Pan
authors.forename: Hong-Chi
authors.initials: HC
authors.lastname: Jiang
authors.forename: Lian-Xin
authors.initials: LX
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D017930:Genes, Reporter; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010087:Oxides / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism; D000071636:Protein Phosphatase 2C; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; C543800:MIRN210 microRNA, human; C543845:MIRN24 microRNA, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D010087:Oxides; C000607458:PPM1D protein, human; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C; D000077237:Arsenic Trioxide