Aberrant Ki-67 expression through 3′UTR alternative polyadenylation in breast cancers

Abstract

Ki-67 (MKI67) is a marker of cellular proliferation of cancer. Here, we show that Ki-67 is post-transcriptionally regulated through alternative polyadenylation (APA) and microRNAs in breast cancer. We show that shortening of the Ki-67 3′UTR results in the loss of the binding sites for the suppressive miRNAs and thus renders the transcript with a shortened 3′UTR insusceptible to miRNA-mediated suppression. This APA-mediated shortening of the Ki-67 3′UTR contributes to increased mRNA stability and enhanced translational efficiency. In summary, our results not only highlight the post-transcriptional regulation of Ki-67 involving APA and microRNAs but also suggest that Ki-67 3′UTR disruption could serve as a molecular marker in breast cancer.