title: miR-372 down-regulates the oncogene ATAD2 to influence hepatocellular carcinoma proliferation and metastasis.
abstract: BACKGROUND
  ATAD2 is associated with many cellular processes, such as cell growth, migration and invasion. However, no studies have been conducted on the molecular biological function of the ATAD2 gene in hepatocellular carcinoma (HCC).
  
  
  METHODS
  The protein and mRNA level expression of ATAD2 was examined in tissues and cell lines. Prognostic significance was analyzed by the Kaplan-Meier survival method and Cox regression. ATAD2 knockdown was used to analyze cell proliferation and invasion. The upstream and downstream of ATAD2 was analyzed by RT2 Profiler™ PCR array and luciferasex fluorescence system.
  
  
  RESULTS
  ATAD2 was highly expressed in liver cancer samples and correlated with poor survival. High ATAD2 expression was positively correlated with metastasis (P = 0.005) and was an independent prognostic factor in HCC (P = 0.001). ATAD2 depletion by RNA interference reduced their capacity for invasion and proliferation and led to a G1 phase arrest in vitro. Further study revealed that miR-372 was an upstream target of ATAD2 as miR-372 was bound directly to its 3' untranslated region (3' UTR). In addition, ATAD2 knockdown was found to extremely up-regulate APC expression and down-regulate CTNNA1 at the mRNA level.
  
  
  CONCLUSIONS
  The findings demonstrated that miR-372 suppressed the expression of ATAD2, which was highly expressed in HCC and exerted a proto-oncogene effect in hepatic carcinogenesis. In conclusion, ATAD2 may promote HCC progression.
authors.affiliation: Department of General Surgery, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China. wugang@mail.cmu.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
authors.forename: Haiyang
authors.initials: H
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: He
authors.forename: Yawei
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Lu
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Yu
authors.forename: Shuguan
authors.initials: S
authors.lastname: Xia
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Meng
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions; D000074183:ATPases Associated with Diverse Cellular Activities; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D001483:Base Sequence; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D063868:Patient Outcome Assessment; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D034741:RNA, Small Interfering; D047368:Tumor Burden; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D025601:Adenomatous Polyposis Coli Protein; C495273:CTNNA1 protein, human; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; C561021:MIRN372 microRNA, human; D035683:MicroRNAs; D000090063:Proto-Oncogene Mas; D034741:RNA, Small Interfering; D051178:alpha Catenin; D000251:Adenosine Triphosphatases; C544857:ATAD2 protein, human; D000074183:ATPases Associated with Diverse Cellular Activities