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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

TitleMicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor
Authors
Issue Date2012
PublisherBMJ Publishing Group. The Journal's web site is located at http://gut.bmjjournals.com/
Citation
Gut, 2012, v. 61 n. 1, p. 33-42 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/144525
ISSN
2014 Impact Factor: 14.660
ISI Accession Number ID
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).

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorKong, KLen_HK
dc.contributor.authorKwong, DLWen_HK
dc.contributor.authorChan, THMen_HK
dc.contributor.authorLaw, SYKen_HK
dc.contributor.authorChen, Len_HK
dc.contributor.authorLi, Yen_HK
dc.contributor.authorQin, YRen_HK
dc.contributor.authorGuan, XYen_HK
dc.date.accessioned2012-02-03T06:12:23Z-
dc.date.available2012-02-03T06:12:23Z-
dc.date.issued2012en_HK
dc.identifier.citationGut, 2012, v. 61 n. 1, p. 33-42en_HK
dc.identifier.issn0017-5749en_HK
dc.identifier.urihttp://hdl.handle.net/10722/144525-
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.en_HK
dc.languageengen_US
dc.publisherBMJ Publishing Group. The Journal's web site is located at http://gut.bmjjournals.com/en_HK
dc.relation.ispartofGuten_HK
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 receptoren_HK
dc.typeArticleen_HK
dc.identifier.emailKwong, DLW: dlwkwong@hku.hken_HK
dc.identifier.emailLaw, SYK: slaw@hku.hken_HK
dc.identifier.emailGuan, XY: xyguan@hkucc.hku.hken_HK
dc.identifier.authorityKwong, DLW=rp00414en_HK
dc.identifier.authorityLaw, SYK=rp00437en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1136/gutjnl-2011-300178en_HK
dc.identifier.pmid21813472en_HK
dc.identifier.scopuseid_2-s2.0-83555177355en_HK
dc.identifier.hkuros194831en_US
dc.identifier.hkuros198359en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-83555177355&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume61en_HK
dc.identifier.issue1en_HK
dc.identifier.spage33en_HK
dc.identifier.epage42en_HK
dc.identifier.eissn1468-3288-
dc.identifier.isiWOS:000298179200005-
dc.publisher.placeUnited Kingdomen_HK
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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.identifier.scopusauthoridKong, KL=36106004300en_HK
dc.identifier.scopusauthoridKwong, DLW=15744231600en_HK
dc.identifier.scopusauthoridChan, THM=26431726400en_HK
dc.identifier.scopusauthoridLaw, SYK=7202241293en_HK
dc.identifier.scopusauthoridChen, L=23569135400en_HK
dc.identifier.scopusauthoridLi, Y=36078298200en_HK
dc.identifier.scopusauthoridQin, YR=7403100680en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK

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