File Download
  • No File Attached
 
Links for fulltext
(May Require Subscription)
 
Supplementary

Article: Deregulated miR-155 promotes Fas-mediated apoptosis in human intervertebral disc degeneration by targeting FADD and caspase-3
  • Basic View
  • Metadata View
  • XML View
TitleDeregulated miR-155 promotes Fas-mediated apoptosis in human intervertebral disc degeneration by targeting FADD and caspase-3
 
AuthorsWang, HQ1
Yu, XD1
Liu, ZH1
Cheng, X3
Samartzis, D2
Jia, LT3
Wu, SX3
Huang, J3
Chen, J3
Luo, ZJ1
 
Keywordsapoptosis
caspase-3
disc degeneration
FADD
miR-155
miRNAs
nucleus pulposus
 
Issue Date2011
 
PublisherJohn Wiley & Sons. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/1130
 
CitationJournal Of Pathology, 2011, v. 225 n. 2, p. 232-242 [How to Cite?]
DOI: http://dx.doi.org/10.1002/path.2931
 
AbstractThe role of apoptosis in the pathogenesis of intervertebral disc degeneration (IDD) remains enigmatic. Accumulating evidence has shown that the apoptotic machinery is regulated by miRNAs. We hypothesized that miRNAs might contribute to apoptosis in IDD. We have found that 29 miRNAs were differentially expressed and miR-155 was down-regulated in degenerative nucleus pulposus (NP). The deregulation of miR-155 was further verified using real-time PCR (0.56 fold, p < 0.05). Bioinformatics target prediction identified FADD and caspase-3 as putative targets of miR-155. Furthermore, miR-155 inhibited FADD and caspase-3 expression by directly targeting their 3′-UTRs, which was abolished by mutation of the miR-155 binding sites. In vitro up-regulation of miR-155 in human NP cells by transfection with lentiviral pre-miR-155 resulted in repression of FADD and caspase-3; whereas knockdown of miR-155 with lentiviral antigomiR-155 led to over-expression of FADD and caspase-3. Also, Fas-mediated apoptosis was increased when antagonizing miR-155 and decreased when using pre-miR-155 in human NP cells. In addition, we presented direct evidence of NP cells undergoing apoptosis in IDD tissues using transmission electron microscopy analysis. Moreover, a combination of in situ hybridization (ISH) and immunohistochemistry (IHC) revealed that miR-155 expressed in the cytoplasm of human NP cells with reverse correlation with FADD and caspase-3. In summary, this is the first study addressing the underlying mechanisms of IDD in terms of apoptosis and miRNAs. Furthermore, caspase-3 is identified as a novel target of miR-155. Our results suggest that deregulated miR-155 promotes Fas-mediated apoptosis in human IDD by targeting FADD and caspase-3, implicating an aetiological and therapeutic role of miR-155 in IDD. Copyright © 2011 Pathological Society of Great Britain and Ireland. Copyright © 2011 Pathological Society of Great Britain and Ireland.
 
ISSN0022-3417
2013 Impact Factor: 7.330
 
DOIhttp://dx.doi.org/10.1002/path.2931
 
ISI Accession Number IDWOS:000295393400011
Funding AgencyGrant Number
Chinese National Natural Science Foundation30901509
30770571
30973052
Key Technologies R&D Programme of Shaanxi Province2008K10-02
Chinese National Basic Research Program2009CB521700
Funding Information:

This study was supported by the Chinese National Natural Science Foundation (Grant Nos 30901509, 30770571 and 30973052), the Key Technologies R&D Programme of Shaanxi Province (Grant No. 2008K10-02) and the Chinese National Basic Research Program (Grant No. 2009CB521700). We thank Dr Yan-Yan Wei for her assistance in ISH and IHC staining; our clinical staff for helping obtain specimens; our office secretary Dan Geng for her coordination of the experimentation; laboratory members Li-Feng Lan, Jie Wu and Jing Li for their assistance in the experimentation; and Kang Chen Bio-tech (Shanghai, China) for their skillful assistance on microRNA microarray.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorWang, HQ
 
dc.contributor.authorYu, XD
 
dc.contributor.authorLiu, ZH
 
dc.contributor.authorCheng, X
 
dc.contributor.authorSamartzis, D
 
dc.contributor.authorJia, LT
 
dc.contributor.authorWu, SX
 
dc.contributor.authorHuang, J
 
dc.contributor.authorChen, J
 
dc.contributor.authorLuo, ZJ
 
dc.date.accessioned2011-08-26T14:25:18Z
 
dc.date.available2011-08-26T14:25:18Z
 
dc.date.issued2011
 
dc.description.abstractThe role of apoptosis in the pathogenesis of intervertebral disc degeneration (IDD) remains enigmatic. Accumulating evidence has shown that the apoptotic machinery is regulated by miRNAs. We hypothesized that miRNAs might contribute to apoptosis in IDD. We have found that 29 miRNAs were differentially expressed and miR-155 was down-regulated in degenerative nucleus pulposus (NP). The deregulation of miR-155 was further verified using real-time PCR (0.56 fold, p < 0.05). Bioinformatics target prediction identified FADD and caspase-3 as putative targets of miR-155. Furthermore, miR-155 inhibited FADD and caspase-3 expression by directly targeting their 3′-UTRs, which was abolished by mutation of the miR-155 binding sites. In vitro up-regulation of miR-155 in human NP cells by transfection with lentiviral pre-miR-155 resulted in repression of FADD and caspase-3; whereas knockdown of miR-155 with lentiviral antigomiR-155 led to over-expression of FADD and caspase-3. Also, Fas-mediated apoptosis was increased when antagonizing miR-155 and decreased when using pre-miR-155 in human NP cells. In addition, we presented direct evidence of NP cells undergoing apoptosis in IDD tissues using transmission electron microscopy analysis. Moreover, a combination of in situ hybridization (ISH) and immunohistochemistry (IHC) revealed that miR-155 expressed in the cytoplasm of human NP cells with reverse correlation with FADD and caspase-3. In summary, this is the first study addressing the underlying mechanisms of IDD in terms of apoptosis and miRNAs. Furthermore, caspase-3 is identified as a novel target of miR-155. Our results suggest that deregulated miR-155 promotes Fas-mediated apoptosis in human IDD by targeting FADD and caspase-3, implicating an aetiological and therapeutic role of miR-155 in IDD. Copyright © 2011 Pathological Society of Great Britain and Ireland. Copyright © 2011 Pathological Society of Great Britain and Ireland.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationJournal Of Pathology, 2011, v. 225 n. 2, p. 232-242 [How to Cite?]
DOI: http://dx.doi.org/10.1002/path.2931
 
dc.identifier.doihttp://dx.doi.org/10.1002/path.2931
 
dc.identifier.epage242
 
dc.identifier.hkuros189129
 
dc.identifier.isiWOS:000295393400011
Funding AgencyGrant Number
Chinese National Natural Science Foundation30901509
30770571
30973052
Key Technologies R&D Programme of Shaanxi Province2008K10-02
Chinese National Basic Research Program2009CB521700
Funding Information:

This study was supported by the Chinese National Natural Science Foundation (Grant Nos 30901509, 30770571 and 30973052), the Key Technologies R&D Programme of Shaanxi Province (Grant No. 2008K10-02) and the Chinese National Basic Research Program (Grant No. 2009CB521700). We thank Dr Yan-Yan Wei for her assistance in ISH and IHC staining; our clinical staff for helping obtain specimens; our office secretary Dan Geng for her coordination of the experimentation; laboratory members Li-Feng Lan, Jie Wu and Jing Li for their assistance in the experimentation; and Kang Chen Bio-tech (Shanghai, China) for their skillful assistance on microRNA microarray.

 
dc.identifier.issn0022-3417
2013 Impact Factor: 7.330
 
dc.identifier.issue2
 
dc.identifier.openurl
 
dc.identifier.pmid21706480
 
dc.identifier.scopuseid_2-s2.0-80052460614
 
dc.identifier.spage232
 
dc.identifier.urihttp://hdl.handle.net/10722/137446
 
dc.identifier.volume225
 
dc.languageeng
 
dc.publisherJohn Wiley & Sons. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/1130
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofJournal of Pathology
 
dc.relation.referencesReferences in Scopus
 
dc.rightsJournal of Pathology. Copyright © John Wiley & Sons.
 
dc.subjectapoptosis
 
dc.subjectcaspase-3
 
dc.subjectdisc degeneration
 
dc.subjectFADD
 
dc.subjectmiR-155
 
dc.subjectmiRNAs
 
dc.subjectnucleus pulposus
 
dc.titleDeregulated miR-155 promotes Fas-mediated apoptosis in human intervertebral disc degeneration by targeting FADD and caspase-3
 
dc.typeArticle
 
<?xml encoding="utf-8" version="1.0"?>
<item><contributor.author>Wang, HQ</contributor.author>
<contributor.author>Yu, XD</contributor.author>
<contributor.author>Liu, ZH</contributor.author>
<contributor.author>Cheng, X</contributor.author>
<contributor.author>Samartzis, D</contributor.author>
<contributor.author>Jia, LT</contributor.author>
<contributor.author>Wu, SX</contributor.author>
<contributor.author>Huang, J</contributor.author>
<contributor.author>Chen, J</contributor.author>
<contributor.author>Luo, ZJ</contributor.author>
<date.accessioned>2011-08-26T14:25:18Z</date.accessioned>
<date.available>2011-08-26T14:25:18Z</date.available>
<date.issued>2011</date.issued>
<identifier.citation>Journal Of Pathology, 2011, v. 225 n. 2, p. 232-242</identifier.citation>
<identifier.issn>0022-3417</identifier.issn>
<identifier.uri>http://hdl.handle.net/10722/137446</identifier.uri>
<description.abstract>The role of apoptosis in the pathogenesis of intervertebral disc degeneration (IDD) remains enigmatic. Accumulating evidence has shown that the apoptotic machinery is regulated by miRNAs. We hypothesized that miRNAs might contribute to apoptosis in IDD. We have found that 29 miRNAs were differentially expressed and miR-155 was down-regulated in degenerative nucleus pulposus (NP). The deregulation of miR-155 was further verified using real-time PCR (0.56 fold, p &lt; 0.05). Bioinformatics target prediction identified FADD and caspase-3 as putative targets of miR-155. Furthermore, miR-155 inhibited FADD and caspase-3 expression by directly targeting their 3&#8242;-UTRs, which was abolished by mutation of the miR-155 binding sites. In vitro up-regulation of miR-155 in human NP cells by transfection with lentiviral pre-miR-155 resulted in repression of FADD and caspase-3; whereas knockdown of miR-155 with lentiviral antigomiR-155 led to over-expression of FADD and caspase-3. Also, Fas-mediated apoptosis was increased when antagonizing miR-155 and decreased when using pre-miR-155 in human NP cells. In addition, we presented direct evidence of NP cells undergoing apoptosis in IDD tissues using transmission electron microscopy analysis. Moreover, a combination of in situ hybridization (ISH) and immunohistochemistry (IHC) revealed that miR-155 expressed in the cytoplasm of human NP cells with reverse correlation with FADD and caspase-3. In summary, this is the first study addressing the underlying mechanisms of IDD in terms of apoptosis and miRNAs. Furthermore, caspase-3 is identified as a novel target of miR-155. Our results suggest that deregulated miR-155 promotes Fas-mediated apoptosis in human IDD by targeting FADD and caspase-3, implicating an aetiological and therapeutic role of miR-155 in IDD. Copyright &#169; 2011 Pathological Society of Great Britain and Ireland. Copyright &#169; 2011 Pathological Society of Great Britain and Ireland.</description.abstract>
<language>eng</language>
<publisher>John Wiley &amp; Sons. The Journal&apos;s web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/1130</publisher>
<relation.ispartof>Journal of Pathology</relation.ispartof>
<rights>Journal of Pathology. Copyright &#169; John Wiley &amp; Sons.</rights>
<subject>apoptosis</subject>
<subject>caspase-3</subject>
<subject>disc degeneration</subject>
<subject>FADD</subject>
<subject>miR-155</subject>
<subject>miRNAs</subject>
<subject>nucleus pulposus</subject>
<title>Deregulated miR-155 promotes Fas-mediated apoptosis in human intervertebral disc degeneration by targeting FADD and caspase-3</title>
<type>Article</type>
<identifier.openurl>http://library.hku.hk:4550/resserv?sid=HKU:IR&amp;issn=0022-3417&amp;volume=225&amp;issue=2&amp;spage=232&#8211;242&amp;epage=&amp;date=2011&amp;atitle=Deregulated+miR-155+promotes+Fas-mediated+apoptosis+in+human+intervertebral+disc+degeneration+by+targeting+FADD+and+caspase-3</identifier.openurl>
<description.nature>link_to_subscribed_fulltext</description.nature>
<identifier.doi>10.1002/path.2931</identifier.doi>
<identifier.pmid>21706480</identifier.pmid>
<identifier.scopus>eid_2-s2.0-80052460614</identifier.scopus>
<identifier.hkuros>189129</identifier.hkuros>
<relation.references>http://www.scopus.com/mlt/select.url?eid=2-s2.0-80052460614&amp;selection=ref&amp;src=s&amp;origin=recordpage</relation.references>
<identifier.volume>225</identifier.volume>
<identifier.issue>2</identifier.issue>
<identifier.spage>232</identifier.spage>
<identifier.epage>242</identifier.epage>
<identifier.isi>WOS:000295393400011</identifier.isi>
<publisher.place>United Kingdom</publisher.place>
</item>
Author Affiliations
  1. Xijing Hospital
  2. The University of Hong Kong
  3. The Fourth Military Medical University