File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: NF-κB targets miR-16 and miR-21 in gastric cancer: Involvement of prostaglandin E receptors

TitleNF-κB targets miR-16 and miR-21 in gastric cancer: Involvement of prostaglandin E receptors
Authors
Issue Date2011
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
Citation
Carcinogenesis, 2011, v. 32 n. 2, p. 240-245 How to Cite?
AbstractCigarette smoke is one of the risk factors for gastric cancer and nicotine has been reported to promote tumor growth. Deregulation of microRNA (miRNA) and cyclooxygenase-2 (COX-2) expressions are hallmarks of many cancers including gastric cancer. Here, we used an miRNA array platform covering a panel of 95 human miRNAs to examine the expression profile in nicotine-treated gastric cancer cells. We found that miR-16 and miR-21 were upregulated upon nicotine stimulation, transfection with anti-miR-16 or anti-miR-21 significantly abrogated cell proliferation. In contrast, ectopic miR-16 or miR-21 expression exhibited a similar stimulatory effect on cell proliferation as nicotine. Nicotine-mediated IkappaBα degradation and nuclear factor-kappa B (NF-κB) translocation dose-dependently. Knockdown of NF-κB by short interfering RNA (siRNA) or specific inhibitor (Bay-11-7085) markedly suppressed nicotine-induced cell proliferation and upregulation of miR-16 and miR-21. Interestingly, NF-κB-binding sites were located in both miR-16 and miR-21 gene transcriptional elements and we showed that nicotine enhanced the binding of NF-κB to the promoters of miR-16 and miR-21. Furthermore, activation of COX-2/prostaglandin E 2 (PGE 2) signaling in response to nicotine was mediated by the action of prostaglandin E receptors (EP2 and EP4). EP2 or EP4 siRNA or antagonists impaired the nicotine-mediated NF-κB activity, upregulation of miR-16 and miR-21 and cell proliferation. Taken together, these results suggest that miR-16 and miR-21 are directly regulated by the transcription factor NF-κB and yet nicotine-promoted cell proliferation is mediated via EP2/4 receptors. Perhaps this study may shed light on the development of anticancer drugs to improve the chemosensitivity in smokers. © The Author 2010. Published by Oxford University Press. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/142524
ISSN
2015 Impact Factor: 4.874
2015 SCImago Journal Rankings: 2.439
ISI Accession Number ID
Funding AgencyGrant Number
University Research Committee (URC)
University of Hong Kong
Chinese University of Hong KongCUHK04/CRF/08
Funding Information:

Small Project Funding from University Research Committee (URC), the University of Hong Kong and funding from the Collaborative Research Fund from the Chinese University of Hong Kong (CUHK04/CRF/08).

References

 

DC FieldValueLanguage
dc.contributor.authorShin, VYen_HK
dc.contributor.authorJin, Hen_HK
dc.contributor.authorNg, EKOen_HK
dc.contributor.authorCheng, ASLen_HK
dc.contributor.authorChong, WWSen_HK
dc.contributor.authorWong, CYPen_HK
dc.contributor.authorLeung, WKen_HK
dc.contributor.authorSung, JJYen_HK
dc.contributor.authorChu, KMen_HK
dc.date.accessioned2011-10-28T02:50:27Z-
dc.date.available2011-10-28T02:50:27Z-
dc.date.issued2011en_HK
dc.identifier.citationCarcinogenesis, 2011, v. 32 n. 2, p. 240-245en_HK
dc.identifier.issn0143-3334en_HK
dc.identifier.urihttp://hdl.handle.net/10722/142524-
dc.description.abstractCigarette smoke is one of the risk factors for gastric cancer and nicotine has been reported to promote tumor growth. Deregulation of microRNA (miRNA) and cyclooxygenase-2 (COX-2) expressions are hallmarks of many cancers including gastric cancer. Here, we used an miRNA array platform covering a panel of 95 human miRNAs to examine the expression profile in nicotine-treated gastric cancer cells. We found that miR-16 and miR-21 were upregulated upon nicotine stimulation, transfection with anti-miR-16 or anti-miR-21 significantly abrogated cell proliferation. In contrast, ectopic miR-16 or miR-21 expression exhibited a similar stimulatory effect on cell proliferation as nicotine. Nicotine-mediated IkappaBα degradation and nuclear factor-kappa B (NF-κB) translocation dose-dependently. Knockdown of NF-κB by short interfering RNA (siRNA) or specific inhibitor (Bay-11-7085) markedly suppressed nicotine-induced cell proliferation and upregulation of miR-16 and miR-21. Interestingly, NF-κB-binding sites were located in both miR-16 and miR-21 gene transcriptional elements and we showed that nicotine enhanced the binding of NF-κB to the promoters of miR-16 and miR-21. Furthermore, activation of COX-2/prostaglandin E 2 (PGE 2) signaling in response to nicotine was mediated by the action of prostaglandin E receptors (EP2 and EP4). EP2 or EP4 siRNA or antagonists impaired the nicotine-mediated NF-κB activity, upregulation of miR-16 and miR-21 and cell proliferation. Taken together, these results suggest that miR-16 and miR-21 are directly regulated by the transcription factor NF-κB and yet nicotine-promoted cell proliferation is mediated via EP2/4 receptors. Perhaps this study may shed light on the development of anticancer drugs to improve the chemosensitivity in smokers. © The Author 2010. Published by Oxford University Press. All rights reserved.en_HK
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/en_HK
dc.relation.ispartofCarcinogenesisen_HK
dc.subject.meshMicroRNAs - physiology-
dc.subject.meshNF-kappa B - physiology-
dc.subject.meshReceptors, Prostaglandin E, EP2 Subtype - physiology-
dc.subject.meshReceptors, Prostaglandin E, EP4 Subtype - physiology-
dc.subject.meshStomach Neoplasms - pathology-
dc.titleNF-κB targets miR-16 and miR-21 in gastric cancer: Involvement of prostaglandin E receptorsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0143-3334&volume=32&issue=2&spage=240&epage=245&date=2011&atitle=NF-κB+targets+miR-16+and+miR-21+in+gastric+cancer:+involvement+of+prostaglandin+E+receptorsen_US
dc.identifier.emailNg, EKO: ngko@hku.hken_HK
dc.identifier.emailLeung, WK: waikleung@hku.hken_HK
dc.identifier.emailChu, KM: chukm@hkucc.hku.hken_HK
dc.identifier.authorityNg, EKO=rp01364en_HK
dc.identifier.authorityLeung, WK=rp01479en_HK
dc.identifier.authorityChu, KM=rp00435en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/carcin/bgq240en_HK
dc.identifier.pmid21081469-
dc.identifier.scopuseid_2-s2.0-79251584345en_HK
dc.identifier.hkuros184333en_US
dc.identifier.hkuros199105en_US
dc.identifier.hkuros198392-
dc.identifier.hkuros210265-
dc.identifier.hkuros184949-
dc.identifier.hkuros206194-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79251584345&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume32en_HK
dc.identifier.issue2en_HK
dc.identifier.spage240en_HK
dc.identifier.epage245en_HK
dc.identifier.isiWOS:000286676400016-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridShin, VY=7003491170en_HK
dc.identifier.scopusauthoridJin, H=24577511700en_HK
dc.identifier.scopusauthoridNg, EKO=21135553700en_HK
dc.identifier.scopusauthoridCheng, ASL=7402075036en_HK
dc.identifier.scopusauthoridChong, WWS=24576241300en_HK
dc.identifier.scopusauthoridWong, CYP=25947838400en_HK
dc.identifier.scopusauthoridLeung, WK=7201504523en_HK
dc.identifier.scopusauthoridSung, JJY=35405352400en_HK
dc.identifier.scopusauthoridChu, KM=7402453538en_HK
dc.identifier.citeulike8757074-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats