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Article: miR-31 is consistently inactivated in EBV-associated nasopharyngeal carcinoma and contributes to its tumorigenesis

TitlemiR-31 is consistently inactivated in EBV-associated nasopharyngeal carcinoma and contributes to its tumorigenesis
Authors
Issue Date2014
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.molecular-cancer.com
Citation
Molecular Cancer , 2014, v. 13 n. 1, p. Article no. 184 How to Cite?
AbstractBACKGROUND: As a distinctive type of head and neck cancers, nasopharyngeal carcinoma (NPC) is genesis from the clonal Epstein-Barr virus (EBV)-infected nasopharyngeal epithelial cells accumulated with multiple genetic lesions. Among the recurrent genetic alterations defined, loss of 9p21.3 is the most frequent early event in the tumorigenesis of EBV-associated NPC. In addition to the reported CDKN2A/p16, herein, we elucidated the role of a miRNA, miR-31 within this 9p21.3 region as NPC-associated tumor suppressor. METHODS: The expression and promoter methylation of miR-31 were assessed in a panel of NPC tumor lines and primary tumors. Its in vitro and in vivo tumor suppression function was investigated through the ectopic expression of miR-31 in NPC cells. We also determined the miR-31 targeted genes and its involvement in the growth in NPC. RESULTS: Downregulation of miR-31 expression was detected in almost all NPC cell line, patient-derived xenografts (PDXs) and primary tumors. Both homozygous deletion and promoter hypermethylation were shown to be major mechanisms for miR-31 silencing in this cancer. Strikingly, loss of miR-31 was also obviously observed in the dysplastic lesions of nasopharynx. Restoration of miR-31 in C666-1 cells inhibited the cell proliferation, colony-forming and migratory capacities. Dramatic reduction of in vitro anchorage-independent growth and in vivo tumorigenic potential were demonstrated in the stable clones expressing miR-31. Furthermore, we proved that miR-31 suppressed the NPC cell growth via targeting FIH1 and MCM2. CONCLUSIONS: The findings provide strong evidence to support miR-31 as a new NPC-associated tumor suppressor on 9p21.3 region. The inactivation of miR-31 may contribute to the early development of NPC.
Persistent Identifierhttp://hdl.handle.net/10722/202506
ISSN
2015 Impact Factor: 5.888
2015 SCImago Journal Rankings: 2.337
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCheung, CCM-
dc.contributor.authorChung, GTY-
dc.contributor.authorLun, SWM-
dc.contributor.authorTo, KF-
dc.contributor.authorChoy, KW-
dc.contributor.authorLau, KM-
dc.contributor.authorSiu, SPK-
dc.contributor.authorGuan, X-
dc.contributor.authorNgan, RKC-
dc.contributor.authorYip, TTC-
dc.contributor.authorBusson, P-
dc.contributor.authorTsao, GSW-
dc.contributor.authorLo, KW-
dc.date.accessioned2014-09-19T08:08:28Z-
dc.date.available2014-09-19T08:08:28Z-
dc.date.issued2014-
dc.identifier.citationMolecular Cancer , 2014, v. 13 n. 1, p. Article no. 184-
dc.identifier.issn1476-4598-
dc.identifier.urihttp://hdl.handle.net/10722/202506-
dc.description.abstractBACKGROUND: As a distinctive type of head and neck cancers, nasopharyngeal carcinoma (NPC) is genesis from the clonal Epstein-Barr virus (EBV)-infected nasopharyngeal epithelial cells accumulated with multiple genetic lesions. Among the recurrent genetic alterations defined, loss of 9p21.3 is the most frequent early event in the tumorigenesis of EBV-associated NPC. In addition to the reported CDKN2A/p16, herein, we elucidated the role of a miRNA, miR-31 within this 9p21.3 region as NPC-associated tumor suppressor. METHODS: The expression and promoter methylation of miR-31 were assessed in a panel of NPC tumor lines and primary tumors. Its in vitro and in vivo tumor suppression function was investigated through the ectopic expression of miR-31 in NPC cells. We also determined the miR-31 targeted genes and its involvement in the growth in NPC. RESULTS: Downregulation of miR-31 expression was detected in almost all NPC cell line, patient-derived xenografts (PDXs) and primary tumors. Both homozygous deletion and promoter hypermethylation were shown to be major mechanisms for miR-31 silencing in this cancer. Strikingly, loss of miR-31 was also obviously observed in the dysplastic lesions of nasopharynx. Restoration of miR-31 in C666-1 cells inhibited the cell proliferation, colony-forming and migratory capacities. Dramatic reduction of in vitro anchorage-independent growth and in vivo tumorigenic potential were demonstrated in the stable clones expressing miR-31. Furthermore, we proved that miR-31 suppressed the NPC cell growth via targeting FIH1 and MCM2. CONCLUSIONS: The findings provide strong evidence to support miR-31 as a new NPC-associated tumor suppressor on 9p21.3 region. The inactivation of miR-31 may contribute to the early development of NPC.-
dc.languageeng-
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.molecular-cancer.com-
dc.relation.ispartofMolecular Cancer-
dc.rightsMolecular Cancer . Copyright © BioMed Central Ltd.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titlemiR-31 is consistently inactivated in EBV-associated nasopharyngeal carcinoma and contributes to its tumorigenesis-
dc.typeArticle-
dc.identifier.emailGuan, X: xyguan@hkucc.hku.hk-
dc.identifier.emailTsao, GSW: gswtsao@hku.hk-
dc.identifier.authorityGuan, X=rp00454-
dc.identifier.authorityTsao, GSW=rp00399-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/1476-4598-13-184-
dc.identifier.pmid25098679-
dc.identifier.pmcidPMC4127521-
dc.identifier.scopuseid_2-s2.0-84905822076-
dc.identifier.hkuros239745-
dc.identifier.volume13-
dc.identifier.issue1-
dc.identifier.spageArticle no. 184-
dc.identifier.epageArticle no. 184-
dc.identifier.isiWOS:000340920000001-
dc.publisher.placeUnited Kingdom-

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