title: TIP60-miR-22 axis as a prognostic marker of breast cancer progression.
abstract: 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.
authors.affiliation: Cancer Science Institute of Singapore, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Pandey
authors.affiliation: Cancer Science Institute of Singapore, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Yanzhou
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore.
authors.forename: Siting
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Cancer Science Institute of Singapore, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore.
authors.forename: Greg
authors.initials: G
authors.lastname: Tucker-Kellogg
authors.affiliation: Cancer Science Institute of Singapore, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Henry
authors.initials: H
authors.lastname: Yang
authors.affiliation: Cancer Science Institute of Singapore, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.|Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Sudhakar
authors.initials: S
authors.lastname: Jha
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D051548:Histone Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D000074443:Lysine Acetyltransferase 5; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics*; D018613:Microscopy, Confocal; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; C548375:MIRN22 microRNA, human; D035683:MicroRNAs; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5
keywords: EMT; KAT5; TIP60; cancer; miR-22