title: Downregulation of miR-610 promotes proliferation and tumorigenicity and activates Wnt/β-catenin signaling in human hepatocellular carcinoma.
abstract: BACKGROUND
  Wnt/β-catenin signaling pathway plays important roles in human cancer progression. Better understanding the mechanism underlying regulation of Wnt/β-catenin signaling pathway might provide novel therapeutic targets for cancer treatment.
  
  
  METHODS
  miR-610 expression levels in hepatocellular carcinoma (HCC) cell lines, HCC tissues and 76 archived HCC specimens were determined using real-time PCR. Cell viability was measured by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. The level of DNA synthesis was determined by BrdU incorporation assay. Flow cytometry analysis was used to analyze cell cycle progression. The cells proliferation and tumorigenesis were determined by colony formation and anchorage-independent growth assays in vitro, and by xenograft tumors in vivo. Luciferase assay and micro-ribonucleoprotein complex immunoprecipitation assay were used to confirm the association of the targeted mRNAs with miR-610.
  
  
  RESULTS
  miR-610 was downregulated in human HCC cells and tissues, and correlated with HCC progression and patient survival. Inhibition of miR-610 promoted, but overexpression of miR-610 reduced, HCC cell proliferation and tumorigenicity both in vitro and in vivo. Furthermore, we found that inhibiting miR-610 activated, but overexpressing miR-610 decreased, the Wnt/β-catenin activity through directly suppressing lipoprotein receptor-related protein 6 (LRP6) and transducin β-like protein 1 (TBL1X). The in vitro analysis was consistent with the inverse correlation detected between miR-610 levels with expression of LRP6 and TBL1X in a cohort of human HCC samples.
  
  
  CONCLUSIONS
  Our results indicate that miR-610 downregulation plays essential roles in HCC progression and reduced miR-610 is correlated with Wnt/β-catenin signaling pathway.
authors.forename: Xian-Cheng
authors.initials: XC
authors.lastname: Zeng
authors.forename: Fo-Qiu
authors.initials: FQ
authors.lastname: Liu
authors.forename: Rong
authors.initials: R
authors.lastname: Yan
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Yi
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tian He Road, Tian He District, Guangzhou, Guangdong 310630, China. njiang163@163.com.
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
mesh_terms: D063646:Carcinogenesis / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D015293:Transducin / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics*
chemical_list: C495270:CTNNB1 protein, human; C555475:LRP6 protein, human; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C575383:MIRN610 microRNA, human; D035683:MicroRNAs; C119542:TBL1X protein, human; D051176:beta Catenin; D015293:Transducin