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Article: Primate-specific microRNA-637 inhibits tumorigenesis in hepatocellular carcinoma by disrupting signal transducer and activator of transcription 3 signaling

TitlePrimate-specific microRNA-637 inhibits tumorigenesis in hepatocellular carcinoma by disrupting signal transducer and activator of transcription 3 signaling
Authors
Issue Date2011
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
Citation
Hepatology, 2011, v. 54 n. 6, p. 2137-2148 How to Cite?
Abstract
MiR-637 (microRNA-637) is a primate-specific miRNA belonging to the small noncoding RNA family, which represses gene regulation at the post-transcriptional expression level. Although it was discovered approximately 5 years ago, its biomedical significance and regulatory mechanism remain obscure. Our preliminary data showed that miR-637 was significantly suppressed in four HCC cell lines and, also, in most of the hepatocellular carcinoma (HCC) specimens, thereby suggesting that miR-637 would be a tumor suppressor in HCC. Simultaneously, the enforced overexpression of miR-637 dramatically inhibited cell growth and induced the apoptosis of HCC cells. The transcription factor, signal transducer and activator of transcription 3 (Stat3), is constitutively activated in multiple tumors, and aberrant Stat3 activation is linked to the promotion of growth and desensitization of apoptosis. Our study showed that Stat3 tyrosine 705 phosphorylation and several Stat3-regulated antiapoptotic genes were down-regulated in miR-637 mimics-transfected and Lv-miR637-infected HCC cells. In addition, miR-637 overexpression negatively regulated Stat3 phosphorylation by suppressing autocrine leukemia inhibitory factor (LIF) expression and exogenous LIF-triggered Stat3 activation and rescued cell growth in these cells. A nude mice model also demonstrated the above-described results, which were obtained from the cell model. Furthermore, we found that LIF was highly expressed in a large proportion of HCC specimens, and its expression was inversely associated with miR-637 expression. Conclusion: Our data indicate that miR-637 acted as a tumor suppressor in HCC, and the suppressive effect was mediated, at least in part, by the disruption of Stat3 activation. (HEPATOLOGY 2011) © 2011 American Association for the Study of Liver Diseases.
Persistent Identifierhttp://hdl.handle.net/10722/168592
ISSN
2013 Impact Factor: 11.190
ISI Accession Number ID
References

 

Author Affiliations
  1. Prince of Wales Hospital Hong Kong
  2. Sun Yat-Sen University
  3. Guangzhou Medical College
  4. Chinese University of Hong Kong
DC FieldValueLanguage
dc.contributor.authorZhang, JFen_US
dc.contributor.authorHe, MLen_US
dc.contributor.authorFu, WMen_US
dc.contributor.authorWang, Hen_US
dc.contributor.authorChen, LZen_US
dc.contributor.authorZhu, Xen_US
dc.contributor.authorChen, Yen_US
dc.contributor.authorXie, Den_US
dc.contributor.authorLai, Pen_US
dc.contributor.authorChen, Gen_US
dc.contributor.authorLu, Gen_US
dc.contributor.authorLin, MCen_US
dc.contributor.authorKung, HFen_US
dc.date.accessioned2012-10-08T03:21:15Z-
dc.date.available2012-10-08T03:21:15Z-
dc.date.issued2011en_US
dc.identifier.citationHepatology, 2011, v. 54 n. 6, p. 2137-2148en_US
dc.identifier.issn0270-9139en_US
dc.identifier.urihttp://hdl.handle.net/10722/168592-
dc.description.abstractMiR-637 (microRNA-637) is a primate-specific miRNA belonging to the small noncoding RNA family, which represses gene regulation at the post-transcriptional expression level. Although it was discovered approximately 5 years ago, its biomedical significance and regulatory mechanism remain obscure. Our preliminary data showed that miR-637 was significantly suppressed in four HCC cell lines and, also, in most of the hepatocellular carcinoma (HCC) specimens, thereby suggesting that miR-637 would be a tumor suppressor in HCC. Simultaneously, the enforced overexpression of miR-637 dramatically inhibited cell growth and induced the apoptosis of HCC cells. The transcription factor, signal transducer and activator of transcription 3 (Stat3), is constitutively activated in multiple tumors, and aberrant Stat3 activation is linked to the promotion of growth and desensitization of apoptosis. Our study showed that Stat3 tyrosine 705 phosphorylation and several Stat3-regulated antiapoptotic genes were down-regulated in miR-637 mimics-transfected and Lv-miR637-infected HCC cells. In addition, miR-637 overexpression negatively regulated Stat3 phosphorylation by suppressing autocrine leukemia inhibitory factor (LIF) expression and exogenous LIF-triggered Stat3 activation and rescued cell growth in these cells. A nude mice model also demonstrated the above-described results, which were obtained from the cell model. Furthermore, we found that LIF was highly expressed in a large proportion of HCC specimens, and its expression was inversely associated with miR-637 expression. Conclusion: Our data indicate that miR-637 acted as a tumor suppressor in HCC, and the suppressive effect was mediated, at least in part, by the disruption of Stat3 activation. (HEPATOLOGY 2011) © 2011 American Association for the Study of Liver Diseases.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/en_US
dc.relation.ispartofHepatologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshApoptosis - Drug Effectsen_US
dc.subject.meshCarcinoma, Hepatocellular - Genetics - Physiopathologyen_US
dc.subject.meshCell Enlargement - Drug Effectsen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshFemaleen_US
dc.subject.meshHep G2 Cellsen_US
dc.subject.meshHumansen_US
dc.subject.meshLeukemia Inhibitory Factor - Antagonists & Inhibitors - Biosynthesis - Drug Effectsen_US
dc.subject.meshLiver Neoplasms - Genetics - Physiopathologyen_US
dc.subject.meshMaleen_US
dc.subject.meshMiceen_US
dc.subject.meshMicrornas - Biosynthesis - Physiologyen_US
dc.subject.meshPrimatesen_US
dc.subject.meshStat3 Transcription Factor - Antagonists & Inhibitorsen_US
dc.subject.meshSignal Transduction - Drug Effectsen_US
dc.subject.meshUp-Regulationen_US
dc.titlePrimate-specific microRNA-637 inhibits tumorigenesis in hepatocellular carcinoma by disrupting signal transducer and activator of transcription 3 signalingen_US
dc.typeArticleen_US
dc.identifier.emailLin, MC:mcllin@hkucc.hku.hken_US
dc.identifier.authorityLin, MC=rp00746en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1002/hep.24595en_US
dc.identifier.pmid21809363en_US
dc.identifier.scopuseid_2-s2.0-82455171626en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-82455171626&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume54en_US
dc.identifier.issue6en_US
dc.identifier.spage2137en_US
dc.identifier.epage2148en_US
dc.identifier.isiWOS:000297974900026-
dc.publisher.placeUnited Statesen_US
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dc.identifier.scopusauthoridZhang, JF=13007942600en_US
dc.identifier.scopusauthoridHe, ML=35080389700en_US
dc.identifier.scopusauthoridFu, WM=52463551200en_US
dc.identifier.scopusauthoridWang, H=7501747965en_US
dc.identifier.scopusauthoridChen, LZ=54379751500en_US
dc.identifier.scopusauthoridZhu, X=34869035800en_US
dc.identifier.scopusauthoridChen, Y=35227073300en_US
dc.identifier.scopusauthoridXie, D=35070710200en_US
dc.identifier.scopusauthoridLai, P=7202946421en_US
dc.identifier.scopusauthoridChen, G=7406541194en_US
dc.identifier.scopusauthoridLu, G=36619108300en_US
dc.identifier.scopusauthoridLin, MC=7404816359en_US
dc.identifier.scopusauthoridKung, HF=7402514190en_US

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