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Published on: March 14, 2019
TIP60-miR-22 axis as a prognostic marker of breast cancer progression
Amit Kumar Pandey1, Yanzhou Zhang1, Siting Zhang2
1Cancer Science Institute of Singapore, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
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.
Insights
MicroRNAs (miRNAs) regulate gene expression and are implicated in diseases like cancer. This study reveals miR-22 targets TIP60, with their imbalance correlating to poor breast cancer survival and metastasis.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- MicroRNAs (miRNAs) are small non-coding RNAs controlling gene expression, with dysregulation linked to diseases such as cancer.
- miR-22 is upregulated in metastatic cancers, potentially promoting stemness and metastasis.
- TIP60, a lysine acetyltransferase, is downregulated in cancer, but the mechanism remains unclear.
Purpose of the Study:
- To identify TIP60 as a direct target of miR-22.
- To investigate the correlation between miR-22 and TIP60 expression in breast cancer patients.
- To explore the role of the miR-22/TIP60 axis in cancer progression and metastasis.
Main Methods:
- Expression correlation analysis in breast cancer patient datasets.
- Bioinformatic pathway analysis to link miR-22/TIP60 to epithelial-mesenchymal transition (EMT).
- In vitro experiments involving blocking endogenous miR-22 to assess TIP60 restoration and cancer cell migration/invasion.
Main Results:
- TIP60 is identified as a direct target of miR-22.
- A negative correlation between TIP60 and miR-22 expression was observed in breast cancer patients.
- High miR-22/low TIP60 levels are associated with poor overall survival and increased cancer cell migration and invasion.
Conclusions:
- The study provides mechanistic insight into TIP60 regulation by miR-22.
- The miR-22/TIP60 axis is implicated in epithelial-mesenchymal transition (EMT) and breast cancer progression.
- Combined assessment of TIP60 and miR-22 may serve as a prognostic indicator for breast cancer.
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