title: [Regulatory role of serum miR-224 in invasiveness and metastasis of cholangiocarcinoma].
abstract: OBJECTIVE
  To investigate the expression profile of serum micro (mi)RNAs in cholangiocarcinoma (CCA) and investigate the regulatory contribution of miRNAs to the invasive and metastasis.
  
  
  METHODS
  Microarray analysis was carried out using serum samples collected from 30 patients with CCA, bile duct cancer tissues and the corresponding normal tissues collected from 10 patients, and serum samples from 50 healthy volunteers. The miRNAs identified as dysregulated in CCA were verified by RT-PCR. Focused analysis on miR-224 was carried out using the human CCA cell lines HCCC-9810 and RBE to investigate the role of this miRNA in IL-6 expression (using IL-6 induction), cell growth, invasiveness and metastasis (using miR-224 mimic transfection). The one-way ANOVA test was used for statistical analysis.
  
  
  RESULTS
  Forty-three miRNAs were dysregulated in CCA (vs. non-CCA, P<0.01), of which 22 were upregulated and 21 were downregulated. RT-PCR data showed that the miR-224 was significantly upregulated in serum as well as in cancer tissue from CCA patients. Induction of HCCC-9810 and RBE cells with IL-6 showed a time-dependent upregulation of miR-224. Furthermore, the HCCC-9810 and RBE cells transfected with miR-224 mimic showed enhanced cell growth, invasiveness and migratory ability.
  
  
  CONCLUSIONS
  IL-6 may promote the invasive and metastatic properties of CCA through upregulated miR-224. Studies of the differentially expressed serum miRNAs in CCA may help to further elucidate the pathogenic processes of this disease and aid in the development of a novel and effective therapeutic strategy.
authors.affiliation: Department of Gastroenterology, Wuxi People's Hospital Affiliated of Nanjing Medical University, Wuxi 214023, China.
authors.forename: Mindan
authors.initials: M
authors.lastname: Huang
authors.forename: Xiongbo
authors.initials: X
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Cao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhan
authors.forename: Min
authors.initials: M
authors.lastname: Xia
authors.forename: Qunyan
authors.initials: Q
authors.lastname: Zhou
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Cai
authors.forename: Fangmei
authors.initials: F
authors.lastname: An
mesh_terms: D001653:Bile Ducts, Intrahepatic; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018281:Cholangiocarcinoma; D015536:Down-Regulation; D006801:Humans; D015850:Interleukin-6; D035683:MicroRNAs; D046228:Microarray Analysis; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D014162:Transfection; D015854:Up-Regulation
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; C546140:MIRN224 microRNA, human; D035683:MicroRNAs