E-Poster Presentation 33rd Lorne Cancer Conference 2021

The impact of miR-21 on miRNA expression in head and neck cancer (#112)

Meredith Hill 1 , Nham Tran 1 2
  1. School of Biomedical Engineering, Faculty of Engineering and IT, University of Technology Sydney, Ultimo, NSW, Australia
  2. The Sydney Head and Neck Cancer Institute, Sydney Cancer Centre, Royal Prince Alfred Hospital, Camperdown, 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 bind to the 3ยด untranslated region (UTR) of mRNA. However, several studies have demonstrated that miRNAs are capable of regulating other miRNAs, known as a miRNA-miRNA interaction. These may occur by: 1) miRNA recognising a binding site within the preliminary form of another miRNA, 2) the direct interaction between two mature miRNAs, and 3) miRNA driven transcription factor regulation.

These modes of miRNA regulation are unexplored in the context of HNSCC. Our lab sought to determine potential miRNA-miRNA interactions initiated by miR-21, which is a major oncomiR in many cancers. Using a miRNA microarray on HNSCC cells transfected with miR-21, we measured the expression of 750 miRNAs and identified those that were dysregulated.

From this analysis we identified a range of dysregulated miRNAs in response to miR-21, such as miR-100, miR-31 and miR-92a. A network of these miRNAs was created to identify potential mechanistic pathways for their dysregulation, and their involvement in major cancer processes. The clinical impact of these miRNAs was investigated using HNSCC patient samples in the Cancer Genome Atlas (TCGA). It showed a potential relationship between miR-21 and the expression of miR-92a and miR-100. We also overexpressed miR-21 in selected HNSCC cell lines to confirm these associations.

In conclusion, we determined that miR-21 is capable of altering the miRNA landscape in HNSCC. It is likely that miR-21 has a similar affect in other cancers due it is prominent levels. These findings imply that miRNA-miRNA regulation may have an important role in cancer gene regulation, thus expanding the cellular role of miRNAs.