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

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TitlePrimate-specific microRNA-637 inhibits tumorigenesis in hepatocellular carcinoma by disrupting signal transducer and activator of transcription 3 signaling
AuthorsZhang, JF3
He, ML3
Fu, WM3
Wang, H3
Chen, LZ1
Zhu, X2
Chen, Y3
Xie, D1
Lai, P3
Chen, G3
Lu, G3
Lin, MC3
Kung, HF3
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
2011 Impact Factor: 11.665
2011 SCImago Journal Rankings: 1.278
DOIhttp://dx.doi.org/10.1002/hep.24595
ReferencesReferences in Scopus
DC Field
Value
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_subscribed_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.issn0270-9139
2011 Impact Factor: 11.665
2011 SCImago Journal Rankings: 1.278
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
Author Affiliations
  1. Sun Yat-Sen University
  2. Guangzhou Medical College
  3. Chinese University of Hong Kong