| Experiment ID | EXP00312 |
| Reference | Title: Regulation of the tumour suppressor PDCD4 by miR-499 and miR-21 in oropharyngeal cancers. Author: Zhang X, Gee H, Rose B, Lee CS, Clark J,Elliott M, Gamble JR, Cairns MJ, Harris A, Khoury S, TranN. Journal: BMC Cancer. 2016 Feb 11;16:86. doi: 10.1186/s12885-016-2109-4. Abstract: BACKGROUND: The rates of oropharyngeal cancers such as tonsil cancers areincreasing. The tumour suppressor protein Programmed Cell Death Protein 4 (PDCD4)has been implicated in the development of various human cancers and small RNAssuch as microRNAs (miRNAs) can regulate its expression. However the exactregulation 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 thetonsillar region, we identified a miRNA profile differentiating SCC tissue fromnormal. Both miR-21 and miR-499 were highly expressed in tonsil SCC tissuesdisplaying 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 wasmediated 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 tonsilSCC 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 tumoursuppressor gene regulation and suggest that PDCD4 loss may be an important stepin tonsillar carcinogenesis. PMID: 26867589 |
| Expressiion Profile | Description: Tonsil cancer compared with normal tonsil tissue Organism: Homo sapiens GEO ID: GSE75630 Platform: GPL21198 Number of samples: 46 |
| Design and Sample | Cancer Type: tonsil cancer Cancer SubType: N/D Cell Line: N/D Experimental Design: cancer vs normal Case Sample: tonsil cancer Control Sample: normal tonsil Num of Case: 28 Num of Control: 18 Quantification Software: Limma Num of miRNAs: 314 |
| Identification | Num of Up: 88 Num of Down: 87 |