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Background:  Both epithelial-to-mesenchymal transition (EMT) and cancer stem cells play important roles in development and progression of breast cancer. MicroRNA (miR)-30 family members have been reported to be associated with the regulation of EMT and stem cell phenotypes, however, the underlying molecular mechanisms are not well understood.   Methods:  miR-30a stable transfectants of breast cancer cell lines were created using a lentiviral system. Bioinformatics analysis was performed to explore miR-30a target genes and SOX4 was selected and identified by dual luciferase reporter assay. The effects of miR-30a and target gene SOX4 on EMT and CSC phenotypes in breast cancer were explored  in vitro  and  in vivo .   Results:  Overexpression of miR-30a in breast cancer cells inhibited EMT and CSC phenotypes by targeting SOX4. Luciferase reporter assay confirmed that miR-30a directly targeted 3'UTR of SOX4, and formed a double-negative feedback loop with SOX4. Functional experiments demonstrated that knockdown of SOX4 suppressed EMT and CSC phenotypes of breast cancer cells through TGF-β/SMAD pathway, which was consistent with the inhibitory effects by overexpression of miR-30a. Additionally, we found disulfiram can upregulate miR-30a expression, and high miR-30a expression was associated with a good prognosis in breast cancer patients through TCGA database.   Conclusion:  Our findings suggest a novel double-negative loop between miR-30a and SOX4 mediated regulation of EMT and CSC features in breast cancer through TGF-β/SMAD pathway, highlighting a novel therapeutic target for breast cancer.

miR-30a/SOX4 Double Negative Feedback Loop is modulated by Disulfiram and regulates EMT and Stem Cell-like properties in Breast Cancer