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Title: TIP60-miR-22 axis as a prognostic marker of breast cancer progression
Authors: Pandey, A.K 
Zhang, Y 
Zhang, S
Li, Y 
Tucker-Kellogg, G 
Yang, H 
Jha, S 
Keywords: acyltransferase
messenger RNA
microRNA 22
protein TIP60
unclassified drug
3' untranslated region
histone acetyltransferase
KAT5 protein, human
MIRN22 microRNA, human
tumor marker
3' untranslated region
breast cancer
breast cancer cell line
cancer growth
cancer patient
cancer prognosis
cell invasion
controlled study
disease association
epithelial mesenchymal transition
gene expression
genetic transfection
human cell
migration inhibition
overall survival
protein analysis
protein expression
protein targeting
breast tumor
cell line
cell motion
confocal microscopy
disease course
gene expression regulation
HEK293 cell line
Kaplan Meier method
MCF-7 cell line
reverse transcription polymerase chain reaction
tumor cell line
3' Untranslated Regions
Biomarkers, Tumor
Breast Neoplasms
Cell Line
Cell Line, Tumor
Cell Movement
Disease Progression
Epithelial-Mesenchymal Transition
Gene Expression Regulation, Neoplastic
HEK293 Cells
Histone Acetyltransferases
Kaplan-Meier Estimate
MCF-7 Cells
Microscopy, Confocal
Reverse Transcriptase Polymerase Chain Reaction
Issue Date: 2015
Citation: Pandey, A.K, Zhang, Y, Zhang, S, Li, Y, Tucker-Kellogg, G, Yang, H, Jha, S (2015). TIP60-miR-22 axis as a prognostic marker of breast cancer progression. Oncotarget 6 (38) : 41290-41306. ScholarBank@NUS Repository.
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 acetyltransferase 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.
Source Title: Oncotarget
ISSN: 19492553
DOI: 10.18632/oncotarget.5636
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