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Article: The putative tumour suppressor microRNA-124 modulates hepatocellular carcinoma cell aggressiveness by repressing ROCK2 and EZH2

TitleThe putative tumour suppressor microRNA-124 modulates hepatocellular carcinoma cell aggressiveness by repressing ROCK2 and EZH2
Authors
Issue Date2012
PublisherBMJ Publishing Group. The Journal's web site is located at http://gut.bmjjournals.com/
Citation
Gut, 2012, v. 61 n. 2, p. 278-289 How to Cite?
Abstract
BACKGROUND: Recent profile studies of microRNA (miRNA) expression have documented a deregulation of miRNA (miR-124) in hepatocellular carcinoma (HCC). OBJECTIVE: To determine the status of miR-124 expression and its underlying mechanisms in the pathogenesis of HCC. METHODS: The expression levels of miR-124 were first examined in HCC cell lines and tumour tissues by real-time PCR. The in vitro and in vivo functional effect of miR-124 was examined further. A luciferase reporter assay was conducted to confirm target associations. RESULTS: The expression levels of miR-124 were frequently reduced in HCC cells and tissues, and low-level expression of miR-124 was significantly associated with a more aggressive and/or poor prognostic phenotype of patients with HCC (p<0.05). In HCC cell lines, stable overexpression of miR-124 was sufficient to inhibit cell motility and invasion in vitro, and suppress intrahepatic and pulmonary metastasis in vivo. In addition, ectopic overexpression of miR-124 in HCC cells inhibited epithelial-mesenchymal cell transition, formation of stress fibres, filopodia and lamellipodia. Further studies showed that miR-124 could directly target the 3'-untranslated region (3'-UTR) of both ROCK2 and EZH2 mRNAs, and suppress their mRNA and protein expressions. These findings suggest that miR-124 plays a critical role in regulating cytoskeletal events and epithelial-mesenchymal cell transition and, ultimately, inhibits the invasive and/or metastatic potential of HCC, probably by its direct target on ROCK2 and EZH2 genes. These results provide functional and mechanistic links between the tumour suppressor miRNA-124 and the two oncogenes ROCK2 and EZH2 on the aggressive nature of HCC. CONCLUSION: These data highlight an important role for miR-124 in the regulation of invasion and metastasis in the molecular aetiology of HCC, and suggest a potential application of miR-124 in prognosis prediction and cancer treatment.
Persistent Identifierhttp://hdl.handle.net/10722/150845
ISSN
2013 Impact Factor: 13.319
ISI Accession Number ID
Funding AgencyGrant Number
973 project of China2010CB529400
2010CB912802
863 project of China2007AA021901
Guangzhou Science and Technology Bureau Foundation2005Z1-E0131
Funding Information:

This study was supported by grants made under the 973 project of China (Nos 2010CB529400 and 2010CB912802) and the 863 project of China (No 2007AA021901), and by a grant from the Guangzhou Science and Technology Bureau Foundation (No 2005Z1-E0131).

References

 

Author Affiliations
  1. Guangdong Provincial People's Hospital
  2. Sun Yat-Sen University
  3. Third Military Medical University
  4. Chinese University of Hong Kong
DC FieldValueLanguage
dc.contributor.authorZheng, Fen_HK
dc.contributor.authorLiao, YJen_HK
dc.contributor.authorCai, MYen_HK
dc.contributor.authorLiu, YHen_HK
dc.contributor.authorLiu, THen_HK
dc.contributor.authorChen, SPen_HK
dc.contributor.authorBian, XWen_HK
dc.contributor.authorGuan, XYen_HK
dc.contributor.authorLin, MCen_HK
dc.contributor.authorZeng, YXen_HK
dc.contributor.authorKung, HFen_HK
dc.contributor.authorXie, Den_HK
dc.date.accessioned2012-06-26T06:12:09Z-
dc.date.available2012-06-26T06:12:09Z-
dc.date.issued2012en_HK
dc.identifier.citationGut, 2012, v. 61 n. 2, p. 278-289en_HK
dc.identifier.issn0017-5749en_HK
dc.identifier.urihttp://hdl.handle.net/10722/150845-
dc.description.abstractBACKGROUND: Recent profile studies of microRNA (miRNA) expression have documented a deregulation of miRNA (miR-124) in hepatocellular carcinoma (HCC). OBJECTIVE: To determine the status of miR-124 expression and its underlying mechanisms in the pathogenesis of HCC. METHODS: The expression levels of miR-124 were first examined in HCC cell lines and tumour tissues by real-time PCR. The in vitro and in vivo functional effect of miR-124 was examined further. A luciferase reporter assay was conducted to confirm target associations. RESULTS: The expression levels of miR-124 were frequently reduced in HCC cells and tissues, and low-level expression of miR-124 was significantly associated with a more aggressive and/or poor prognostic phenotype of patients with HCC (p<0.05). In HCC cell lines, stable overexpression of miR-124 was sufficient to inhibit cell motility and invasion in vitro, and suppress intrahepatic and pulmonary metastasis in vivo. In addition, ectopic overexpression of miR-124 in HCC cells inhibited epithelial-mesenchymal cell transition, formation of stress fibres, filopodia and lamellipodia. Further studies showed that miR-124 could directly target the 3'-untranslated region (3'-UTR) of both ROCK2 and EZH2 mRNAs, and suppress their mRNA and protein expressions. These findings suggest that miR-124 plays a critical role in regulating cytoskeletal events and epithelial-mesenchymal cell transition and, ultimately, inhibits the invasive and/or metastatic potential of HCC, probably by its direct target on ROCK2 and EZH2 genes. These results provide functional and mechanistic links between the tumour suppressor miRNA-124 and the two oncogenes ROCK2 and EZH2 on the aggressive nature of HCC. CONCLUSION: These data highlight an important role for miR-124 in the regulation of invasion and metastasis in the molecular aetiology of HCC, and suggest a potential application of miR-124 in prognosis prediction and cancer treatment.en_HK
dc.languageengen_US
dc.publisherBMJ Publishing Group. The Journal's web site is located at http://gut.bmjjournals.com/en_HK
dc.relation.ispartofGuten_HK
dc.rightsGut. Copyright © BMJ Publishing Group.-
dc.rightsThis article has been accepted for publication in [Gut]. The definitive copyedited, typeset version [Gut, 2012, v. 61 n. 2, p. 278-289] is available online at: www.gut.bmj.com-
dc.subject.meshCarcinoma, Hepatocellular - metabolism - pathologyen_US
dc.subject.meshDNA-Binding Proteins - metabolismen_US
dc.subject.meshLiver Neoplasms - metabolism - pathologyen_US
dc.subject.meshMicroRNAs - metabolismen_US
dc.subject.meshTranscription Factors - metabolismen_US
dc.titleThe putative tumour suppressor microRNA-124 modulates hepatocellular carcinoma cell aggressiveness by repressing ROCK2 and EZH2en_HK
dc.typeArticleen_HK
dc.identifier.emailGuan, XY: xyguan@hkucc.hku.hken_HK
dc.identifier.emailXie, D: xied@mail.sysu.edu.cnen_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.identifier.authorityLin, MC=rp00746en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1136/gut.2011.239145en_HK
dc.identifier.pmid21672940en_HK
dc.identifier.scopuseid_2-s2.0-84855191863en_HK
dc.identifier.hkuros203476-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84855191863&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume61en_HK
dc.identifier.issue2en_HK
dc.identifier.spage278en_HK
dc.identifier.epage289en_HK
dc.identifier.isiWOS:000298665000017-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridXie, D=35070710200en_HK
dc.identifier.scopusauthoridKung, HF=7402514190en_HK
dc.identifier.scopusauthoridZeng, YX=7402981579en_HK
dc.identifier.scopusauthoridLin, MC=7404816359en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK
dc.identifier.scopusauthoridBian, XW=7103023096en_HK
dc.identifier.scopusauthoridChen, SP=39761180800en_HK
dc.identifier.scopusauthoridLiu, TH=36091417000en_HK
dc.identifier.scopusauthoridLiu, YH=36014503900en_HK
dc.identifier.scopusauthoridCai, MY=23388510500en_HK
dc.identifier.scopusauthoridLiao, YJ=36114448500en_HK
dc.identifier.scopusauthoridZheng, F=39462354900en_HK

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