title: microRNA-141 inhibits cell proliferation and invasion and promotes apoptosis by targeting hepatocyte nuclear factor-3β in hepatocellular carcinoma cells.
abstract: BACKGROUND
  Hepatocyte nuclear factor-3β (HNF-3β) plays a critical role in hepatocyte differentiation and controls liver-specific gene expression during the development of hepatocellular carcinoma (HCC), but the molecular basis of this process has not been fully elucidated. microRNAs (miRNAs) are powerful, post-transcriptional regulators of gene expression. Whether miRNAs can impact the effects of HNF-3β in HCC is still unknown.
  
  
  METHODS
  HNF-3β and miR-141 expression levels were detected in HepG2 cells, using real-time quantitative RT-PCR (qRT-PCR). Luciferase reporter assays and Western blots were used to validate HNF-3β as a direct target gene of miR-141. Cell proliferation, invasion, and apoptosis were also examined to confirm whether miR-141 could impact on HNF-3β in HCC.
  
  
  RESULTS
  In this study, we found that HNF-3β protein levels were consistently upregulated in HCC clinical tissues compared with matched normal adjacent tissues. However, the mRNA levels of HNF-3β varied in random tissues, suggesting that a post-transcriptional mechanism was involved in its regulation. We used bioinformatic analyses to search for miRNAs that could potentially target HNF-3β, and identified specific targeting sites for miR-141 in the 3'-untranslated region (3'-UTR) of the HNF-3β gene. By overexpressing miR-141 in HepG2 cells, we experimentally validated that miR-141 directly regulated HNF-3β expression. Furthermore, the biological consequences of targeting HNF-3β by miR-141 were examined using cell proliferation, invasion and apoptosis assays in vitro. We demonstrated that the repression of HNF-3β by miR-141 suppressed the proliferation and invasion and promoted the apoptosis of HepG2 cells.
  
  
  CONCLUSIONS
  miR-141 functions as a tumor suppressor in HCC cells through the inhibition of HNF-3β translation.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Hongwei
authors.initials: H
authors.lastname: Liang
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaomao
authors.initials: X
authors.lastname: Yin
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Hu
authors.forename: Jinlan
authors.initials: J
authors.lastname: Huang
authors.forename: Tingyu
authors.initials: T
authors.lastname: Ren
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, North of Guangzhou avenue No,1838, Baiyun District, Guangzhou 510515, P,R, China. nfyyzhenglei@smu.edu.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D051542:Hepatocyte Nuclear Factor 3-beta / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness
chemical_list: D020413:3' Untranslated Regions; C496502:FOXA2 protein, human; C533895:MIRN141 microRNA, human; D035683:MicroRNAs; D051542:Hepatocyte Nuclear Factor 3-beta