TIP60-miR-22 axis as a prognostic marker of breast cancer progression
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Amit Kumar Pandey1, Yanzhou Zhang1, Siting Zhang3, Ying Li1, Greg Tucker-Kellogg3, Henry Yang1, Sudhakar Jha1,2
1Cancer Science Institute of Singapore, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
2Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
3Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore
Sudhakar Jha, e-mail: email@example.com
Keywords: cancer, TIP60, KAT5, EMT, miR-22
Received: March 30, 2015 Accepted: September 12, 2015 Published: October 19, 2015
MicroRNAs (miRNAs) are 22- to 24-nucleotide, small, non-coding RNAs that bind to the 3′UTR of target genes to control gene expression. Consequently, their dysregulation contributes to many diseases, including diabetes and cancer. miR-22 is up-regulated in numerous metastatic cancers and recent studies have suggested a role for miR-22 in promoting stemness and metastasis. TIP60 is a lysine acetyl-transferase reported to be down-regulated in cancer but the molecular mechanism of this reduction is still unclear. In this study, we identify TIP60 as a target of miR-22. We show a negative correlation in the expression of TIP60 and miR-22 in breast cancer patients, and show that low levels of TIP60 and high levels of miR-22 are associated with poor overall survival. Furthermore, pathway analysis using high miR-22/low TIP60 and low miR-22/high TIP60 breast cancer patient datasets suggests association of TIP60/miR-22 with epithelial-mesenchymal transition (EMT), a key alteration in progression of cancer cells. We show that blocking endogenous miR-22 can restore TIP60 levels, which in turn decreases the migration and invasion capacity of metastatic breast cancer cell line. These results provide mechanistic insight into TIP60 regulation and evidence for the utility of the combination of TIP60 and miR-22 as prognostic indicator of breast cancer progression.
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