miR-21 and miR-499 promote tumor cell migration in head and neck cancer by targeting PDCD4. — The Association Specialists
  1. Schedule
  2. Young Investigator Session
  3. miR-21 and miR-499 promote tumor cell migration in head and neck cancer by targeting PDCD4.

miR-21 and miR-499 promote tumor cell migration in head and neck cancer by targeting PDCD4. (409)

Pamela Ajuyah 1 , Gyorgy Hutvagner 1 2 , Nham Tran 1 2 3
  1. The University of Technology, Sydney, Ultimo, NSW, Australia
  2. Faculty of Engineering and Information Technology, Centre for Health Technologies, Sydney
  3. Sydney Cancer Centre, The Sydney Head and Neck Cancer Institute, Royal Prince Alfred Hospital

Background

MicroRNAs (miRNAs) are small non-coding RNAs which play an important role in tumor metastasis by targeting genes involved in cell migration1. The role of miRNAs in Head and Neck Squamous Cell Carcinoma (HNSCC) is poorly understood2. Our lab has identified miR-21 and miR-499 as key miRNAs, which regulate the tumor suppressor gene PDCD4 in HNSCCs. In this study, we dissect the exact interaction of these miRNAs to the target gene and provide evidence that both miRNAs promote migration of head and neck cancer cells.

Methods

To understand the direct interaction of these miRNAs to PDCD4, mutants were created to represent the four key binding areas and tested using a luciferase reporter. A scratch assay in combination with live cell imaging was then utilised to determine if these miRNAs affected cell migration of HNSCC cell lines.

Results

Both these miRNAs directly regulate PDCD4 expression at specific binding sites. Interestingly, one of the three miR-499 binding sites appears to be critical as mutations at this site abolish silencing activity.  We also found that miR-21 and miR-499 levels can influence the migration of specific HNSCC cell lines. Live cell imaging of HNSCC cells overexpressing miR-21 and miR-499 showed significant increases in their migratory rate. In contrast, inhibition of miR-21 resulted in decreased migration speed.

Conclusion

This study has investigated the function of miRNAs in head and neck cancer. We show that the tumor suppressor PDCD4 is regulated by both miR-21 and miR-499 independently of each other. Overexpression of these miRNAs leads to increased migration and this may represent a novel regulatory pathway for tumor metastases in head and neck cancers.


  1. Pencheva, N. and Tavazole, S.F. (2013). Control of metastatic progression by microRNA regulatory networks. Nature Cell Biology 15, 546-554
  2. Chang, S.S, Jiang, W.W, Smith, I, Poeta, L.M, Begum, S, Glazer, C, Shan, S, Westra, W, Sidransky, D, Califano, J.A (2008). MicroRNA alterations in head and neck squamous cell carcinoma. International Journal of Cancer, 2008. 123, 2791-2797