The Regulation of miR-200c/141 Cluster by HDAC Inhibitors via Polycomb Group Protein BMI1
Open AccessPolycomb group protein BMI1, a known oncogene, is a transcriptional repressor that is overexpressed in several cancers. It plays an important role in regulation of stem cell renewal. MicroRNAs (miRNAs) have emerged as major regulatory genes associated with cancer and can function either as oncogenes or tumor suppressors. At present, very little is known about the pharmacological approaches to inhibit BMI1 and to target miRNAs. Histone deacetylase inhibitors (HDACi) have recently been found to be a promising anti-cancer therapeutics as they regulate various cancer-related phenotypes, including cell proliferation, migration and invasion. In this study, we explored the role of HDACi in regulating BMI1 and miRNAs, specifically miR-200c and miR-141. We report that HDACi promote expression of tumor suppressor miRNAs, miR-200c and miR-141 via downregulation of BMI1. We also show that BMI1 directly binds to miR-200c/141 promoter and regulate it through transcription factor binding motifs, E-box2 and Z-box1 to repress its expression. Previously, it has been reported that miR-200c/141 regulate BMI1 transcriptionally. Therefore, our studies suggest a reciprocal regulation between BMI1 and miR-200c/141 cluster.
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