Investigating miR-23a/b Regulation of KDM6A Protein Expression in Epithelial-Mesenchymal Transition Using Breast Cancer Cell Models

Kim, Joelle
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Tumor progression of epithelial cancers is facilitated by epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET), reverse processes that enable invasive cellular behavior. A key regulator of EMT/MET is lysine (K)-specific demethylase 6A (KDM6A), an activator of epithelial gene expression that is abundant in epithelial cell phenotypes. During EMT progression, the level of KDM6A protein expression decreases but there is no change in KDM6A transcript. Understanding the post-transcriptional regulators of KDM6A may reveal new modulators of EMT and potential therapeutic targets. MicroRNAs are short non-coding RNAs that bind mRNA transcripts to repress protein translation. To identify miRNAs that likely target KDM6A, we utilized seven databases as well as in vitro and clinical data to identify miR-23a and miR-23b as putative regulators of KDM6A. We then overexpressed miR-23a/b in breast cancer cells and, unexpectedly, observed no impact on KDM6A protein expression. Further research may explore other means of post-transcriptional regulation of KDM6A, including additional miRNA screening and alternative splicing analysis.

Epithelial-mesenchymal transition., Cancer metastasis., MicroRNAs., KDM6A., Epigenetic modification., RNA interference.