MiR-30c regulates metastasis and polarity reversal of tumor cell clusters by targeting MTDH in invasive micropapillary carcinoma of the breast

Purpose: Invasive micropapillary carcinoma (IMPC) of the breast has a high propensity for lymphovascular invasion and axillary lymph node metastasis and displays an ‘inside-out’ growth pattern, but the molecular mechanism of metastasis and tumor cell polarity reversal in IMPC is unclear. Methods and Patients: Luciferase reporter assays and western blotting were performed to confirm that the MTDH 3’UTR bound to miR-30c. Growth curves, tumor sphere formation assays, Transwell migration and invasion assays, mouse xenograft model and immunofluorescence were evaluated to investigate the effects of miR-30c and MTDH. MiRNA in situ hybridization (ISH) and immunohistochemistry (IHC) were carried out on IMPC patient tissues for miR-30c and MTDH expression, respectively. Results We found that miR-30c could directly target the MTDH (metadherin) 3’UTR. MiR-30c overexpression inhibited breast cancer cell proliferation, invasion and metastasis by targeting MTDH in vitro and in vivo . Moreover, miR-30c regulated IMPC cell polarity reversal by targeting MTDH. By in situ hybridization and immunohistochemistry analyses, miR-30c and MTDH were significantly correlated with tumor size, lymph nodule status and tumor grade, the ‘inside-out’ growth pattern, overall survival (OS) and disease-free survival (DFS) in IMPC patients (p < 0.05). Conclusions Overall, miR-30c overexpression could inhibit breast cancer cell proliferation and metastasis and regulate polarity reversal by targeting MTDH.