Regulation of the tumour suppressor PDCD4 by miR-499 and miR-21 in oropharyngeal cancers

Zhang, X; Gee, H; Rose, B; Lee, CS; Clark, J; Elliott, M; Gamble, JR; Cairns, MJ; Harris, A; Khoury, S; Tran, N

Regulation of the tumour suppressor PDCD4 by miR-499 and miR-21 in oropharyngeal cancers

Zhang, X Gee, H Rose, B Lee, CS Clark, J Elliott, M Gamble, JR Cairns, MJ Harris, A Khoury, S

Tran, N

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Publication Type:: Journal Article
Citation:: BMC Cancer, 2016, 16 (1)
Issue Date:: 2016-02-11

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Field	Value	Language
dc.contributor.author	Zhang, X	en_US
dc.contributor.author	Gee, H	en_US
dc.contributor.author	Rose, B	en_US
dc.contributor.author	Lee, CS	en_US
dc.contributor.author	Clark, J	en_US
dc.contributor.author	Elliott, M	en_US
dc.contributor.author	Gamble, JR	en_US
dc.contributor.author	Cairns, MJ	en_US
dc.contributor.author	Harris, A	en_US
dc.contributor.author	Khoury, S https://orcid.org/0000-0001-5631-7478	en_US
dc.contributor.author	Tran, N https://orcid.org/0000-0001-7747-2530	en_US
dc.date.available	2016-02-02	en_US
dc.date.issued	2016-02-11	en_US
dc.identifier.citation	BMC Cancer, 2016, 16 (1)	en_US
dc.identifier.uri	http://hdl.handle.net/10453/43237
dc.description.abstract	© 2016 Zhang et al. Background: The rates of oropharyngeal cancers such as tonsil cancers are increasing. The tumour suppressor protein Programmed Cell Death Protein 4 (PDCD4) has been implicated in the development of various human cancers and small RNAs such as microRNAs (miRNAs) can regulate its expression. However the exact regulation of PDCD4 by multiple miRNAs in oropharyngeal squamous cell carcinoma (SCC) is not well understood. Results: Using two independent oropharyngeal SCC cohorts with a focus on the tonsillar region, we identified a miRNA profile differentiating SCC tissue from normal. Both miR-21 and miR-499 were highly expressed in tonsil SCC tissues displaying a loss of PDCD4. Interestingly, expression of the miRNA machinery, Dicer1, Drosha, DDX5 (Dead Box Helicase 5) and DGCR8 (DiGeorge Syndrome Critical Region Gene 8) were all elevated by greater than 2 fold in the tonsil SCC tissue. The 3'UTR of PDCD4 contains three binding-sites for miR-499 and one for miR-21. Using a wild-type and truncated 3'UTR of PDCD4, we demonstrated that the initial suppression of PDCD4 was mediated by miR-21 whilst sustained suppression was mediated by miR-499. Moreover the single miR-21 site was able to elicit the same magnitude of suppression as the three miR-499 sites. Conclusion: This study describes the regulation of PDCD4 specifically in tonsil SCC by miR-499 and miR-21 and has documented the loss of PDCD4 in tonsil SCCs. These findings highlight the complex interplay between miRNAs and tumour suppressor gene regulation and suggest that PDCD4 loss may be an important step in tonsillar carcinogenesis.	en_US
dc.relation.ispartof	BMC Cancer	en_US
dc.relation.isbasedon	10.1186/s12885-016-2109-4	en_US
dc.subject.classification	Oncology & Carcinogenesis	en_US
dc.subject.mesh	Cell Line, Tumor	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Carcinoma, Squamous Cell	en_US
dc.subject.mesh	Oropharyngeal Neoplasms	en_US
dc.subject.mesh	Ribonuclease III	en_US
dc.subject.mesh	RNA-Binding Proteins	en_US
dc.subject.mesh	MicroRNAs	en_US
dc.subject.mesh	Cell Proliferation	en_US
dc.subject.mesh	Gene Expression Regulation, Neoplastic	en_US
dc.subject.mesh	Apoptosis Regulatory Proteins	en_US
dc.subject.mesh	DEAD-box RNA Helicases	en_US
dc.subject.mesh	Carcinogenesis	en_US
dc.title	Regulation of the tumour suppressor PDCD4 by miR-499 and miR-21 in oropharyngeal cancers	en_US
dc.type	Journal Article
utslib.citation.volume	1	en_US
utslib.citation.volume	16	en_US
utslib.for	1112 Oncology and Carcinogenesis	en_US
utslib.for	0903 Biomedical Engineering	en_US
utslib.for	1117 Public Health and Health Services	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access
pubs.issue	1	en_US
pubs.publication-status	Published	en_US
pubs.volume	16	en_US

Abstract:

© 2016 Zhang et al. Background: The rates of oropharyngeal cancers such as tonsil cancers are increasing. The tumour suppressor protein Programmed Cell Death Protein 4 (PDCD4) has been implicated in the development of various human cancers and small RNAs such as microRNAs (miRNAs) can regulate its expression. However the exact regulation of PDCD4 by multiple miRNAs in oropharyngeal squamous cell carcinoma (SCC) is not well understood. Results: Using two independent oropharyngeal SCC cohorts with a focus on the tonsillar region, we identified a miRNA profile differentiating SCC tissue from normal. Both miR-21 and miR-499 were highly expressed in tonsil SCC tissues displaying a loss of PDCD4. Interestingly, expression of the miRNA machinery, Dicer1, Drosha, DDX5 (Dead Box Helicase 5) and DGCR8 (DiGeorge Syndrome Critical Region Gene 8) were all elevated by greater than 2 fold in the tonsil SCC tissue. The 3'UTR of PDCD4 contains three binding-sites for miR-499 and one for miR-21. Using a wild-type and truncated 3'UTR of PDCD4, we demonstrated that the initial suppression of PDCD4 was mediated by miR-21 whilst sustained suppression was mediated by miR-499. Moreover the single miR-21 site was able to elicit the same magnitude of suppression as the three miR-499 sites. Conclusion: This study describes the regulation of PDCD4 specifically in tonsil SCC by miR-499 and miR-21 and has documented the loss of PDCD4 in tonsil SCCs. These findings highlight the complex interplay between miRNAs and tumour suppressor gene regulation and suggest that PDCD4 loss may be an important step in tonsillar carcinogenesis.

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http://hdl.handle.net/10453/43237