The subcutaneous and metastases tumor models were employed to study the effects of miR-22 on cell proliferation and metastasis of breast cancer cells in vivo.
In this study, we demonstrated a moderate elevation in miR-22 expression in the 182<sup>R</sup>-6 fulvestrant-resistant breast cancer line we used as a model system, and this elevation was positively correlated with the expression of the miRNA biogenesis enzymes AGO2 and Dicer.
In conclusion, this study elucidated the roles of miR-22 in regulation of breast cancer differentiation and migration, which provides a target for early diagnose and therapy of breast cancer.
SIRT1 levels were observed to be increased in stage III-IV when compared with stage I-II breast cancer. miR-22 overexpression decreased the proliferation, migration and invasion of MCF-7 cells, whereas overexpression of SIRT1 eliminated the suppressive effects of the miR-22 overexpression on the malignant phenotype of MCF-7 cells.
In contrast to the oncogenic role of miR-22 reported in myelodysplastic syndrome (MDS) and breast cancer, here we show that miR-22 is an essential anti-tumour gatekeeper in de novo acute myeloid leukaemia (AML) where it is significantly downregulated.
Importantly, a beneficial effect of miR-22 on clinical outcomes in breast cancer was shown to depend on the expression levels of the identified target genes, demonstrating the relevance of miRNA/mRNA interactions to disease progression in vivo.
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.