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

Xiaoying Zhang, Harriet Gee, Barbara Rose, C. Soon Lee, Jonathan Clark, Michael Elliott, Jennifer R. Gamble, Murray J. Cairns, Adrian Harris, Samantha Khoury, Nham Tran*

*Corresponding author for this work

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number86
Pages (from-to)1-11
Number of pages11
JournalBMC Cancer
Volume16
Issue number1
DOIs
Publication statusPublished - 11 Feb 2016
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2016. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Fingerprint Dive into the research topics of 'Regulation of the tumour suppressor PDCD4 by miR-499 and miR-21 in oropharyngeal cancers'. Together they form a unique fingerprint.

  • Cite this

    Zhang, X., Gee, H., Rose, B., Lee, C. S., Clark, J., Elliott, M., ... Tran, N. (2016). Regulation of the tumour suppressor PDCD4 by miR-499 and miR-21 in oropharyngeal cancers. BMC Cancer, 16(1), 1-11. [86]. https://doi.org/10.1186/s12885-016-2109-4