Figure 7. Proposed model for the critical roles of miR-320a in the mediation of tamoxifen sensitivity.

P₄ or E₂ specifically promotes or represses miR-320a expression via c-Myc to modulate the expression of ARPP-19, ERRγ, and their downstreams c-Myc, Cyclin D1, which are also directly regulated by E₂. MiR-320a further directly downregulates ARPP-19 and ERRγ, which in turn represses c-Myc expression, and subsequently re-sensitizes tamoxifen-resistant breast cancer cells to tamoxifen. A positive feedback loop is proposed as indicated between c-Myc and miR-320a to regulate tamoxifen resistance in breast cancer.