Objectives:
In this study we tested the hypothesis that specific microRNAs, a class of regulatory non-coding RNA whose expression is altered in OSCC, attenuate the expression of integrins in OSCC leading to changes in cancer cell adhesion, migration and invasion.
Methods:
In silico analysis of publicly available databases was used to identify miRNA capable of binding to the integrin beta-1 (ITGB1) 3' untranslated region (3'UTR). Transient transfection of OSCC in culture with synthetic precursors to miRNA followed by immunoblotting of cell lysates or cell-adhesion assays was utilised to examine regulatory effects.
Results:
Bioinformatic analysis revealed a binding site for miR-124, a microRNA known to be upregulated in OSCC, in the 3'UTR of the ITGB1 transcript. Transfection of a synthetic precursor to mature miR-124 into H357 (OSCC-derived) cells resulted in a significant reduction in the levels of the ITGB1 protein. This change was reflected in a dramatic reduction (>50 %) in the ability of transfected H357 cells to adhere to fibronectin compared with cells transfected with a control oligonucleotide.
Conclusions:
The results of this study reveal a hitherto unidentified role for microRNAs, molecules increasingly recognised as potential prognostic markers and therapeutic targets, in the regulation of ITGB1 expression and function in oral cancer cells.