MicroRNA-144 suppresses cholangiocarcinoma cell proliferation and invasion through targeting platelet activating factor acetylhydrolase isoform 1b

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• 作者：Rui Yang (29) (31)
  Yongjun Chen (29)
  Cong Tang (30)
  Hongbo Li (29)
  Bing Wang (29)
  Qun Yan (29)
  Junbo Hu (29)
  Shengquan Zou (29)
  
  29. Department of General Surgery ; Affiliated Tongji Hospital ; Tongji Medical College of Huazhong University of Science and Technology ; 1095 Jiefang Avenue ; Wuhan ; Hubei ; 430030 ; China
  31. Department of General Surgery ; The Fifth Hospital of Wuhan ; Wuhan ; Hubei ; 430037 ; China
  30. Department of General Surgery ; The Fifth Affiliated Hospital of Sun Yat-sen University ; Zhuhai ; Guangdong ; 519000 ; China
  
• 关键词：CCA ; miRNA ; Cell proliferation ; Cell invasion ; LIS1
• 刊名：BMC Cancer
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：14
• 期：1
• 全文大小：1,859 KB
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  37. The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1471-2407/14/917/prepub
  
• 刊物主题：Cancer Research; Oncology; Stem Cells; Animal Models; Internal Medicine;
• 出版者：BioMed Central
• ISSN：1471-2407

文摘

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.