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Article: MicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor
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TitleMicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor
 
AuthorsKong, KL1
Kwong, DLW1
Chan, THM1
Law, SYK1
Chen, L1
Li, Y1
Qin, YR3
Guan, XY1 2
 
Issue Date2012
 
PublisherBMJ Publishing Group. The Journal's web site is located at http://gut.bmjjournals.com/
 
CitationGut, 2012, v. 61 n. 1, p. 33-42 [How to Cite?]
DOI: http://dx.doi.org/10.1136/gutjnl-2011-300178
 
AbstractBackground: To understand the involvement of micro- RNA (miRNA) in the development and progression of oesophageal squamous cell carcinoma (ESCC), miRNA profiles were compared between tumour and corresponding non-tumour tissues. Methods: miRCURY LNA array was used to generate miRNA expressing profile. Real-time quantitative PCR was applied to detectthe expression of miR-375 in ESCC samples and its correlation with insulin-like growth factor 1 receptor (IGF1R). Methylation-specific PCR was used to study the methylation status in the promoter region of miR-375. The tumour-suppressive effect of miR-375 was determined by both in-vitro and in-vivo assays. Results: The downregulation of miR-375 was frequently detected in primary ESCC, which was significantly correlated with advanced stage (p=0.003), distant metastasis (p<0.0001), poor overall survival (p=0.048) and disease-free survival (p=0.0006). Promoter methylation of miR-375 was detected in 26 of 45 (57.8%) ESCC specimens. Functional assays demonstrated that miR-375 could inhibit clonogenicity, cell motility, cell proliferation, tumour formation and metastasis in mice. Further study showed that miR-375 could interact with the 39-untranslated region of IGF1R and downregulate its expression. In clinical specimens, the expression of IGF1R was also negatively correlated with miR-375 expression (p=0.008). Conclusions: This study demonstrates that miR-375 has a strong tumour-suppressive effect through inhibiting the expression of IGF1R. The downregulation of miR-375, which is mainly caused by promoter methylation, is one of the molecular mechanisms involved in the development and progression of ESCC.
 
ISSN0017-5749
2013 Impact Factor: 13.319
 
DOIhttp://dx.doi.org/10.1136/gutjnl-2011-300178
 
ISI Accession Number IDWOS:000298179200005
Funding AgencyGrant Number
Hong Kong Research Grant Council Central AllocationHKUST 2/06C
National Natural Science Foundation of China30700820
30772475
30971606
Sun Yat-Sen University85000-3171311
Funding Information:

This work was supported by grants from Hong Kong Research Grant Council Central Allocation (HKUST 2/06C); the National Natural Science Foundation of China (30700820, 30772475 and 30971606); and Sun Yat-Sen University 'Hundred Talents Program' (85000-3171311).

 
ReferencesReferences in Scopus
 
GrantsEsophageal Carcinoma Research Center
Esophageal Carcinoma Research Center
Esophageal Carcinoma Research Center
Esophageal Carcinoma Research Center
Esophageal Carcinoma Research Center
Esophageal Carcinoma Research Center
 
DC FieldValue
dc.contributor.authorKong, KL
 
dc.contributor.authorKwong, DLW
 
dc.contributor.authorChan, THM
 
dc.contributor.authorLaw, SYK
 
dc.contributor.authorChen, L
 
dc.contributor.authorLi, Y
 
dc.contributor.authorQin, YR
 
dc.contributor.authorGuan, XY
 
dc.date.accessioned2012-02-03T06:12:23Z
 
dc.date.available2012-02-03T06:12:23Z
 
dc.date.issued2012
 
dc.description.abstractBackground: To understand the involvement of micro- RNA (miRNA) in the development and progression of oesophageal squamous cell carcinoma (ESCC), miRNA profiles were compared between tumour and corresponding non-tumour tissues. Methods: miRCURY LNA array was used to generate miRNA expressing profile. Real-time quantitative PCR was applied to detectthe expression of miR-375 in ESCC samples and its correlation with insulin-like growth factor 1 receptor (IGF1R). Methylation-specific PCR was used to study the methylation status in the promoter region of miR-375. The tumour-suppressive effect of miR-375 was determined by both in-vitro and in-vivo assays. Results: The downregulation of miR-375 was frequently detected in primary ESCC, which was significantly correlated with advanced stage (p=0.003), distant metastasis (p<0.0001), poor overall survival (p=0.048) and disease-free survival (p=0.0006). Promoter methylation of miR-375 was detected in 26 of 45 (57.8%) ESCC specimens. Functional assays demonstrated that miR-375 could inhibit clonogenicity, cell motility, cell proliferation, tumour formation and metastasis in mice. Further study showed that miR-375 could interact with the 39-untranslated region of IGF1R and downregulate its expression. In clinical specimens, the expression of IGF1R was also negatively correlated with miR-375 expression (p=0.008). Conclusions: This study demonstrates that miR-375 has a strong tumour-suppressive effect through inhibiting the expression of IGF1R. The downregulation of miR-375, which is mainly caused by promoter methylation, is one of the molecular mechanisms involved in the development and progression of ESCC.
 
dc.description.naturepublished_or_final_version
 
dc.identifier.citationGut, 2012, v. 61 n. 1, p. 33-42 [How to Cite?]
DOI: http://dx.doi.org/10.1136/gutjnl-2011-300178
 
dc.identifier.doihttp://dx.doi.org/10.1136/gutjnl-2011-300178
 
dc.identifier.eissn1468-3288
 
dc.identifier.epage42
 
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dc.identifier.hkuros194831
 
dc.identifier.hkuros198359
 
dc.identifier.isiWOS:000298179200005
Funding AgencyGrant Number
Hong Kong Research Grant Council Central AllocationHKUST 2/06C
National Natural Science Foundation of China30700820
30772475
30971606
Sun Yat-Sen University85000-3171311
Funding Information:

This work was supported by grants from Hong Kong Research Grant Council Central Allocation (HKUST 2/06C); the National Natural Science Foundation of China (30700820, 30772475 and 30971606); and Sun Yat-Sen University 'Hundred Talents Program' (85000-3171311).

 
dc.identifier.issn0017-5749
2013 Impact Factor: 13.319
 
dc.identifier.issue1
 
dc.identifier.pmid21813472
 
dc.identifier.scopuseid_2-s2.0-83555177355
 
dc.identifier.spage33
 
dc.identifier.urihttp://hdl.handle.net/10722/144525
 
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.projectEsophageal Carcinoma Research Center
 
dc.relation.projectEsophageal Carcinoma Research Center
 
dc.relation.projectEsophageal Carcinoma Research Center
 
dc.relation.projectEsophageal Carcinoma Research Center
 
dc.relation.projectEsophageal Carcinoma Research Center
 
dc.relation.projectEsophageal Carcinoma Research Center
 
dc.relation.referencesReferences in Scopus
 
dc.rightsGut. Copyright © BMJ Publishing Group.
 
dc.rightsAttribution 3.0 Hong Kong License
 
dc.subject.meshCarcinoma, Squamous Cell - genetics - mortality - pathology
 
dc.subject.meshEsophageal Neoplasms - genetics - mortality - pathology
 
dc.subject.meshMicroRNAs - chemistry - metabolism
 
dc.subject.meshReceptor, IGF Type 1 - metabolism
 
dc.subject.meshTumor Markers, Biological - chemistry - metabolism
 
dc.titleMicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong
  2. Sun Yat-Sen University
  3. First Affiliated Hospital of Zhengzhou University