<em>One Man’s Junk is Another Man’s Treasure: Regulation of junk RNA “miRNAs” by HPV16 in oral cancers </em> — University of Technology
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One Man’s Junk is Another Man’s Treasure: Regulation of junk RNA “miRNAs” by HPV16 in oral cancers (14282)

James Chen 1 , Nham Tran 2 3
  1. UTS Faculty of Science, Ultimo, NSW, Australia
  2. The Sydney Head and Neck Cancer Institute, Sydney Cancer Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
  3. Faculty of Engineering and Information Technology, Centre for Health Technologies. Faculty of Engineering and Information Technology. University of Technology, Sydney, Sydney, NSW, Australia

Background

MicroRNAs are small non-coding elements of the genome. Once thought as nothing more than junk genomic material, they are now known to be broad and powerful genetic modifiers and regulators. Human Papillomavirus 16 (HPV16)-a high-risk variant is a known carcinogen and a risk factor for oral squamous cell carcinomas (OSCCs). The oncogenes E6 and E7 drive the tumorigenic process for OSCCs, but their exact role in regulating specific miRNAs is not well characterised.

We hypothesise that HPV16 oncogenes, E6 and E7 may regulate different sets of miRNAs in OSCCs. These oncogenes will alter the expression of the miRNA biogenesis machinery. These miRNA changes alter the gene expression milieu of a normal epithelial cell setting it on a pathway to transformation.

Methods

Constructs encoding E6 and its variants E6*I, E6*II and E7 were generated. These vectors were utilised to develop an in vitro OSCCs cell line model(s) for the transient overexpression of these oncogenes. Cells overexpressing E6, E6*I, E6*II or E7 were harvested at 24 and 48 hrs and the expression of specific miRNAs, TRFs and biogenesis machinery measured at the RNA and protein level.

Results

We transfected two independent OSCC cell lines (UMSCC22B and SCC89) and observed over‑expression of E6, E6*I, E6*II and E7. Using this transient approach, the miRNA biogenesis machinery AGO3, AGO4, Dicer and Drosha were altered in cells over-expressing the E6 oncogene. Specific miRNAs appeared to be regulated by the different HPV16 oncogenes. The change in miRNA expression and machinery was seen to be cell line specific.

Conclusion

We established a cell line model to investigate the regulatory impact of the HPV16 oncogenes E6, E6*I, E6*II and E7. The miRNA biogenesis machinery and specific miRNAs were altered in E6 expressing cells and this change may represent additional mechanisms by which HPV16 uses to induce carcinogenesis.

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