miRNA:miRNA interactions in head and neck squamous cell carcinoma

Hill M1 and Tran N1,2

  1. School of Biomedical Engineering, Faculty of Engineering and IT, University of Technology Sydney, NSW, Australia.
  2. The Sydney Head and Neck Cancer Institute, Sydney Cancer Centre, Royal Prince Alfred Hospital, NSW, Australia.

Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common form of cancer. It is commonly caused by smoking, alcohol, and Human Papilloma Virus (HPV). Due to its recent increase in incidence worldwide, it is important to investigate the molecular mechanisms responsible for HNSCC. MicroRNAs (miRNAs) control messenger RNA (mRNA) and have an important role in disease development. Normally, miRNAs perform their regulatory function by binding to the 3’ untranslated region (UTR) of mRNA. However, several studies have demonstrated that miRNAs are involved in the regulation of other miRNAs, known as a miRNA:miRNA interaction. This mode of regulation is unexplored in HNSCC. Our lab has identified miR-21 and miR-499 as important regulators in HNSCC. The overexpression of miR-21 in HNSCC cells reduced the levels of mature miR-499. However, miR-499 did not alter miR-21 levels. To determine if miR-21 overexpression has any global effect, we measured the expression of 750 miRNAs. From this analysis, both miR-21 and miR-499 overexpression could regulate specific miRNAs such as miR-148, miR-100, and miR-31. This data was then used to create an interactome to visualise the identified miRNA:miRNA interactions and their connections to genes. Furthermore, miR-21 overexpression dysregulated the RNA levels of the biogenesis components, Ago2, Ago3, and Dicer. This has implications on mature miRNA levels, and may affect the regulation of HNSCC related genes. In summary, our study provides the first characterisation of miRNA:miRNA interactions in HNSCC cells, and demonstrates that miR-21 can alter the levels of specific miRNAs and affect expression of the biogenesis machinery.