title: Deregulation of microRNA expression occurs early and accumulates in early stages of HBV-associated multistep hepatocarcinogenesis.
abstract: OBJECTIVE
  Deregulation of microRNAs (miRNAs) plays an important role in human carcinogenesis. However, miRNA deregulation in the pre-malignant lesions and expression changes during multistep hepatocarcinogenesis remain elusive.
  
  
  METHODS
  In this study, we investigated the expression changes of seven cancer-related miRNAs during the early stages of HBV related hepatocarcinogenesis. miRNA was extracted from formalin fixed paraffin embedded (FFPE) dysplastic nodules (DN), small HCCs, and their corresponding non-tumorous livers. Expression changes of miRNAs were examined by real-time RT-qPCR.
  
  
  RESULTS
  We found that down-regulation of miR-145 and miR-199b and up-regulation of miR-224 were frequently observed in pre-malignant DNs and these changes persisted throughout HCC development. Restoration of miR-145 in both HepG2 and Hep3B HCC cells significantly inhibited cell proliferation and reduced cell migration and cell invasion. Furthermore, these inhibitory functions of miR-145 could be substantially reduced by an anti-miR-145 inhibitor.
  
  
  CONCLUSIONS
  Our results showed that miRNA deregulation was an early event and accumulated throughout the various steps of HBV-associated hepatocarcinogenesis. Our findings also suggest that miR-145 is a candidate tumor suppressive miRNA and may play an important role in HCC development.
authors.affiliation: Department of Pathology, Li Ka Shing Faculty Medicine, The University of Hong Kong, Hong Kong, People’s Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.forename: Carmen Chak-Lui
authors.initials: CC
authors.lastname: Wong
authors.forename: Edmund Kwok-Kwan
authors.initials: EK
authors.lastname: Tung
authors.forename: Joyce Man-Fong
authors.initials: JM
authors.lastname: Lee
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Wong
authors.forename: Irene Oi-Lin
authors.initials: IO
authors.lastname: Ng
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000821:virology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003043:Cocarcinogenesis; D005260:Female; D006509:Hepatitis B / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D006515:Hepatitis B virus / Q000472:pathogenicity*; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000821:virology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012334:RNA, Neoplasm / Q000235:genetics* / Q000378:metabolism*
chemical_list: C541010:MIRN145 microRNA, human; C546140:MIRN224 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm; C531408:mirn199 microRNA, human