title: MicroRNA-144 suppresses cholangiocarcinoma cell proliferation and invasion through targeting platelet activating factor acetylhydrolase isoform 1b.
abstract: BACKGROUND
  MicroRNAs are endogenous non-coding RNAs that play important roles in a wide variety of biological processes such as apoptosis, development, aging and cancer. The aberrant expression of miRNAs may contribute to phenotypic features of malignant cells, including resistance to chemotherapy. However, in cholangiocarcinoma (CCA) the correlation between miRNAs and their potential roles in CCA remains unclear.
  
  
  METHODS
  MicroRNA profiles were analyzed in three pairs of CCA tumor specimens and non-tumorous-paired biliary tissues using Agilent microRNA microarrays. Expression of selected miRNAs was further confirmed in CCA tissues and CCA cell lines by q-PCR. The effects of miR-144 were evaluated by cell proliferation, migration, transwell, and tumorigenicity assays. Expression of LIS1 (platelet-activating factor acetylhydrolase isoform 1b) was assessed in CCA specimens and CCA cell lines by q-PCR and western blot. Targeting of LIS1 by miR-144 was confirmed by luciferase reporter assays.
  
  
  RESULTS
  We found that the expression of 28 miRNAs in CCA tissues was significantly different from their corresponding adjacent normal bile duct tissues. We focused on miR-144 which was significantly down-regulated in CCA tissues. Reintroduction of miR-144 in CCA cell lines not only inhibited cell growth, but also significantly reduced cell migration and invasion capacities compared with controls. Luciferase assays and western blots verified LIS1 as a direct target of miR-144, and knocking-down LIS1 has similar effect with overexpression of miR-144 in CCA cell lines. Moreover, overexpression of miR-144 expression could suppress tumor growth in nude mice.
  
  
  CONCLUSIONS
  Our results showed that miR-144 was reduced in CCA tissues and suggested that miR-144 may be an essential suppresser of CCA cell proliferation and invasion through targeting LIS1.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Chen
authors.forename: Cong
authors.initials: C
authors.lastname: Tang
authors.forename: Hongbo
authors.initials: H
authors.lastname: Li
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Qun
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Department of General Surgery, Affiliated Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei 430030, China. jbhu@tjh.tjmu.edu.cn.
authors.forename: Junbo
authors.initials: J
authors.lastname: Hu
authors.forename: Shengquan
authors.initials: S
authors.lastname: Zou
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001650:Bile Duct Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009374:Neoplasms, Experimental; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: C554293:MIRN144 microRNA, human; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human