MiR-30c suppresses the proliferation, 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 invasion, metastasis and cell polarity reversal in IMPC is unclear.

METHODS

and Patients: Cell growth curves, tumor sphere formation assays, transwell assays, mouse xenograft model and immunofluorescence were evaluated to investigate the effects of miR-30c and MTDH. Dual luciferase reporter assays was performed to confirm that the MTDH (metadherin) 3'UTR bound to miR-30c. MiRNA hybridization (ISH) and immunohistochemistry (IHC) were carried out on IMPC patient tissues for miR-30c and MTDH expression, respectively.

RESULTS

We found miR-30c as a tumor suppressor gene in cell proliferation, metastasis and polarity reversal of IMPC. Overexpression of miR-30c inhibited cell growth and metastasis and . MiR-30c could directly target the MTDH 3'UTR. MiR-30c overexpression inhibited breast cancer cell proliferation, invasion and metastasis by targeting MTDH. Moreover, miR-30c/MTDH axis could also regulate cell polarity reversal of IMPC. By ISH and IHC 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.

CONCLUSIONS

Overall, miR-30c/MTDH axis was responsible for tumor proliferation, metastasis and polarity reversal. It may provide promising therapeutic targets and prognostic biomarkers for patients with IMPC.