File Download
 
Links for fulltext
(May Require Subscription)
 
Supplementary

Article: Primate-specific microRNA-637 inhibits tumorigenesis in hepatocellular carcinoma by disrupting signal transducer and activator of transcription 3 signaling
  • Basic View
  • Metadata View
  • XML View
TitlePrimate-specific microRNA-637 inhibits tumorigenesis in hepatocellular carcinoma by disrupting signal transducer and activator of transcription 3 signaling
 
AuthorsZhang, JF4
He, ML4 4
Fu, WM4
Wang, H4
Chen, LZ2
Zhu, X3
Chen, Y4 4
Xie, D2
Lai, P1
Chen, G1
Lu, G1
Lin, MC1
Kung, HF4 4
 
Issue Date2011
 
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
 
CitationHepatology, 2011, v. 54 n. 6, p. 2137-2148 [How to Cite?]
DOI: http://dx.doi.org/10.1002/hep.24595
 
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.
 
ISSN0270-9139
2012 Impact Factor: 12.003
2012 SCImago Journal Rankings: 4.260
 
DOIhttp://dx.doi.org/10.1002/hep.24595
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorZhang, JF
 
dc.contributor.authorHe, ML
 
dc.contributor.authorFu, WM
 
dc.contributor.authorWang, H
 
dc.contributor.authorChen, LZ
 
dc.contributor.authorZhu, X
 
dc.contributor.authorChen, Y
 
dc.contributor.authorXie, D
 
dc.contributor.authorLai, P
 
dc.contributor.authorChen, G
 
dc.contributor.authorLu, G
 
dc.contributor.authorLin, MC
 
dc.contributor.authorKung, HF
 
dc.date.accessioned2012-10-08T03:21:15Z
 
dc.date.available2012-10-08T03:21:15Z
 
dc.date.issued2011
 
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.
 
dc.description.natureLink_to_OA_fulltext
 
dc.identifier.citationHepatology, 2011, v. 54 n. 6, p. 2137-2148 [How to Cite?]
DOI: http://dx.doi.org/10.1002/hep.24595
 
dc.identifier.doihttp://dx.doi.org/10.1002/hep.24595
 
dc.identifier.epage2148
 
dc.identifier.f100012838956
 
dc.identifier.f100012838956
 
dc.identifier.f100012838956
 
dc.identifier.f100012838956
 
dc.identifier.f100012838956
 
dc.identifier.f100012838956
 
dc.identifier.f100012838956
 
dc.identifier.f100012838956
 
dc.identifier.f100012838956
 
dc.identifier.f100012838956
 
dc.identifier.f100012838956
 
dc.identifier.f100012838956
 
dc.identifier.f100012838956
 
dc.identifier.f100012838956
 
dc.identifier.f100012838956
 
dc.identifier.f100012838956
 
dc.identifier.f100012838956
 
dc.identifier.f100012838956
 
dc.identifier.f100012838956
 
dc.identifier.issn0270-9139
2012 Impact Factor: 12.003
2012 SCImago Journal Rankings: 4.260
 
dc.identifier.issue6
 
dc.identifier.pmid21809363
 
dc.identifier.scopuseid_2-s2.0-82455171626
 
dc.identifier.spage2137
 
dc.identifier.urihttp://hdl.handle.net/10722/168592
 
dc.identifier.volume54
 
dc.languageeng
 
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofHepatology
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAnimals
 
dc.subject.meshApoptosis - Drug Effects
 
dc.subject.meshCarcinoma, Hepatocellular - Genetics - Physiopathology
 
dc.subject.meshCell Enlargement - Drug Effects
 
dc.subject.meshCell Line, Tumor
 
dc.subject.meshFemale
 
dc.subject.meshHep G2 Cells
 
dc.subject.meshHumans
 
dc.subject.meshLeukemia Inhibitory Factor - Antagonists & Inhibitors - Biosynthesis - Drug Effects
 
dc.subject.meshLiver Neoplasms - Genetics - Physiopathology
 
dc.subject.meshMale
 
dc.subject.meshMice
 
dc.subject.meshMicrornas - Biosynthesis - Physiology
 
dc.subject.meshPrimates
 
dc.subject.meshStat3 Transcription Factor - Antagonists & Inhibitors
 
dc.subject.meshSignal Transduction - Drug Effects
 
dc.subject.meshUp-Regulation
 
dc.titlePrimate-specific microRNA-637 inhibits tumorigenesis in hepatocellular carcinoma by disrupting signal transducer and activator of transcription 3 signaling
 
dc.typeArticle
 
<?xml encoding="utf-8" version="1.0"?>
<item><contributor.author>Zhang, JF</contributor.author>
<contributor.author>He, ML</contributor.author>
<contributor.author>Fu, WM</contributor.author>
<contributor.author>Wang, H</contributor.author>
<contributor.author>Chen, LZ</contributor.author>
<contributor.author>Zhu, X</contributor.author>
<contributor.author>Chen, Y</contributor.author>
<contributor.author>Xie, D</contributor.author>
<contributor.author>Lai, P</contributor.author>
<contributor.author>Chen, G</contributor.author>
<contributor.author>Lu, G</contributor.author>
<contributor.author>Lin, MC</contributor.author>
<contributor.author>Kung, HF</contributor.author>
<date.accessioned>2012-10-08T03:21:15Z</date.accessioned>
<date.available>2012-10-08T03:21:15Z</date.available>
<date.issued>2011</date.issued>
<identifier.citation>Hepatology, 2011, v. 54 n. 6, p. 2137-2148</identifier.citation>
<identifier.issn>0270-9139</identifier.issn>
<identifier.uri>http://hdl.handle.net/10722/168592</identifier.uri>
<description.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) &#169; 2011 American Association for the Study of Liver Diseases.</description.abstract>
<language>eng</language>
<publisher>John Wiley &amp; Sons, Inc. The Journal&apos;s web site is located at http://www.hepatology.org/</publisher>
<relation.ispartof>Hepatology</relation.ispartof>
<subject.mesh>Animals</subject.mesh>
<subject.mesh>Apoptosis - Drug Effects</subject.mesh>
<subject.mesh>Carcinoma, Hepatocellular - Genetics - Physiopathology</subject.mesh>
<subject.mesh>Cell Enlargement - Drug Effects</subject.mesh>
<subject.mesh>Cell Line, Tumor</subject.mesh>
<subject.mesh>Female</subject.mesh>
<subject.mesh>Hep G2 Cells</subject.mesh>
<subject.mesh>Humans</subject.mesh>
<subject.mesh>Leukemia Inhibitory Factor - Antagonists &amp; Inhibitors - Biosynthesis - Drug Effects</subject.mesh>
<subject.mesh>Liver Neoplasms - Genetics - Physiopathology</subject.mesh>
<subject.mesh>Male</subject.mesh>
<subject.mesh>Mice</subject.mesh>
<subject.mesh>Micrornas - Biosynthesis - Physiology</subject.mesh>
<subject.mesh>Primates</subject.mesh>
<subject.mesh>Stat3 Transcription Factor - Antagonists &amp; Inhibitors</subject.mesh>
<subject.mesh>Signal Transduction - Drug Effects</subject.mesh>
<subject.mesh>Up-Regulation</subject.mesh>
<title>Primate-specific microRNA-637 inhibits tumorigenesis in hepatocellular carcinoma by disrupting signal transducer and activator of transcription 3 signaling</title>
<type>Article</type>
<description.nature>Link_to_OA_fulltext</description.nature>
<identifier.doi>10.1002/hep.24595</identifier.doi>
<identifier.pmid>21809363</identifier.pmid>
<identifier.scopus>eid_2-s2.0-82455171626</identifier.scopus>
<relation.references>http://www.scopus.com/mlt/select.url?eid=2-s2.0-82455171626&amp;selection=ref&amp;src=s&amp;origin=recordpage</relation.references>
<identifier.volume>54</identifier.volume>
<identifier.issue>6</identifier.issue>
<identifier.spage>2137</identifier.spage>
<identifier.epage>2148</identifier.epage>
<publisher.place>United States</publisher.place>
<identifier.f1000>12838956</identifier.f1000>
<identifier.f1000>12838956</identifier.f1000>
<identifier.f1000>12838956</identifier.f1000>
<identifier.f1000>12838956</identifier.f1000>
<identifier.f1000>12838956</identifier.f1000>
<identifier.f1000>12838956</identifier.f1000>
<identifier.f1000>12838956</identifier.f1000>
<identifier.f1000>12838956</identifier.f1000>
<identifier.f1000>12838956</identifier.f1000>
<identifier.f1000>12838956</identifier.f1000>
<identifier.f1000>12838956</identifier.f1000>
<identifier.f1000>12838956</identifier.f1000>
<identifier.f1000>12838956</identifier.f1000>
<identifier.f1000>12838956</identifier.f1000>
<identifier.f1000>12838956</identifier.f1000>
<identifier.f1000>12838956</identifier.f1000>
<identifier.f1000>12838956</identifier.f1000>
<identifier.f1000>12838956</identifier.f1000>
<identifier.f1000>12838956</identifier.f1000>
<bitstream.url>http://hub.hku.hk/bitstream/10722/168592/1/re01.htm</bitstream.url>
</item>
Author Affiliations
  1. Prince of Wales Hospital Hong Kong
  2. Sun Yat-Sen University
  3. Guangzhou Medical College
  4. Chinese University of Hong Kong