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Article: The putative tumour suppressor microRNA-124 modulates hepatocellular carcinoma cell aggressiveness by repressing ROCK2 and EZH2
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TitleThe putative tumour suppressor microRNA-124 modulates hepatocellular carcinoma cell aggressiveness by repressing ROCK2 and EZH2
 
AuthorsZheng, F2 2
Liao, YJ2 2
Cai, MY2 2
Liu, YH1
Liu, TH2 2 2
Chen, SP2 2
Bian, XW3
Guan, XY2 2
Lin, MC4
Zeng, YX2 2
Kung, HF2 4
Xie, D2 2
 
Issue Date2012
 
PublisherBMJ Publishing Group. The Journal's web site is located at http://gut.bmjjournals.com/
 
CitationGut, 2012, v. 61 n. 2, p. 278-289 [How to Cite?]
DOI: http://dx.doi.org/10.1136/gut.2011.239145
 
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.
 
ISSN0017-5749
2012 Impact Factor: 10.732
2012 SCImago Journal Rankings: 3.379
 
DOIhttp://dx.doi.org/10.1136/gut.2011.239145
 
ISI Accession Number IDWOS:000298665000017
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).

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorZheng, F
 
dc.contributor.authorLiao, YJ
 
dc.contributor.authorCai, MY
 
dc.contributor.authorLiu, YH
 
dc.contributor.authorLiu, TH
 
dc.contributor.authorChen, SP
 
dc.contributor.authorBian, XW
 
dc.contributor.authorGuan, XY
 
dc.contributor.authorLin, MC
 
dc.contributor.authorZeng, YX
 
dc.contributor.authorKung, HF
 
dc.contributor.authorXie, D
 
dc.date.accessioned2012-06-26T06:12:09Z
 
dc.date.available2012-06-26T06:12:09Z
 
dc.date.issued2012
 
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.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationGut, 2012, v. 61 n. 2, p. 278-289 [How to Cite?]
DOI: http://dx.doi.org/10.1136/gut.2011.239145
 
dc.identifier.doihttp://dx.doi.org/10.1136/gut.2011.239145
 
dc.identifier.epage289
 
dc.identifier.hkuros203476
 
dc.identifier.isiWOS:000298665000017
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).

 
dc.identifier.issn0017-5749
2012 Impact Factor: 10.732
2012 SCImago Journal Rankings: 3.379
 
dc.identifier.issue2
 
dc.identifier.pmid21672940
 
dc.identifier.scopuseid_2-s2.0-84855191863
 
dc.identifier.spage278
 
dc.identifier.urihttp://hdl.handle.net/10722/150845
 
dc.identifier.volume61
 
dc.languageeng
 
dc.publisherBMJ Publishing Group. The Journal's web site is located at http://gut.bmjjournals.com/
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofGut
 
dc.relation.referencesReferences in Scopus
 
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 - pathology
 
dc.subject.meshDNA-Binding Proteins - metabolism
 
dc.subject.meshLiver Neoplasms - metabolism - pathology
 
dc.subject.meshMicroRNAs - metabolism
 
dc.subject.meshTranscription Factors - metabolism
 
dc.titleThe putative tumour suppressor microRNA-124 modulates hepatocellular carcinoma cell aggressiveness by repressing ROCK2 and EZH2
 
dc.typeArticle
 
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<contributor.author>Cai, MY</contributor.author>
<contributor.author>Liu, YH</contributor.author>
<contributor.author>Liu, TH</contributor.author>
<contributor.author>Chen, SP</contributor.author>
<contributor.author>Bian, XW</contributor.author>
<contributor.author>Guan, XY</contributor.author>
<contributor.author>Lin, MC</contributor.author>
<contributor.author>Zeng, YX</contributor.author>
<contributor.author>Kung, HF</contributor.author>
<contributor.author>Xie, D</contributor.author>
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<description.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&lt;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&apos;-untranslated region (3&apos;-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.</description.abstract>
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<subject.mesh>Carcinoma, Hepatocellular - metabolism - pathology</subject.mesh>
<subject.mesh>DNA-Binding Proteins - metabolism</subject.mesh>
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Author Affiliations
  1. Guangdong Provincial People's Hospital
  2. Sun Yat-Sen University
  3. Third Military Medical University
  4. Chinese University of Hong Kong