miR‐191/DAB2 axis regulates the tumorigenicity of estrogen receptor‐positive breast cancer

Disabled‐2 (DAB2) has been shown to be downregulated in a variety of human cancer types including breast tumors. However, the role of DAB2 in estrogen receptor positive (ER+) breast cancer cells has not been reported. In this context, we demonstrated that DAB2 expression was significantly decreased in ER+ breast cancer cell lines and ER+ clinical specimens, compared with ER– breast cancer cell lines and ER– tissues, respectively. Depletion of estrogen significantly elevated DAB2 expression in ER+ MCF7 and T‐47D cells. Treatment with estradiol (E2) reduced the expression of DAB2 and administration of tamoxifen upregulated DAB2 expression in a dose‐dependent manner. Functionally, silencing of DAB2 in hormone‐starved MCF7 and T‐47D cells promoted cellular proliferation and enforced expression of DAB2 in normal‐cultured or E2‐treated cells suppressed cellular proliferation. Mechanistically, estrogen‐induced miR‐191 was identified as a direct upstream regulator of DAB2 in ER+ cells. Luciferase reporter assay indicated that miR‐191 inhibited DAB2 expression by directly targeting the 3′‐UTR of DAB2. Importantly, the expression and function of miR‐191 showed the opposite tendency with DAB2 in ER+ cells. In vivo , inhibition of miR‐191 significantly suppressed the xenograft growth induced by E2, and silencing of DAB2 could restored the growth arrest induced by miR‐191 inhibition. Taken together, our data unveil that the miR‐191‐DAB2 axis seems to be an important pathway associated with estrogen signaling in breast cancer and may serve as a potential diagnostic biomarker and a powerful therapeutic target for ER+ breast cancer patients. © 2017 IUBMB Life, 70(1):71–80, 2018