miR-613 Suppresses Chemoresistance and Stemness in Triple-Negative Breast Cancer by Targeting FAM83A

Introduction: Triple-negative breast Cancer (TNBC) is the most aggressive malignancy of breast Cancer, which represents about 20% of all cases. The prognosis of TNBC remains unfavorable due to the lack of targeted therapy and chemoresistance. The aim of this study is to investigate the role of miR-613 in TNBC.

Material and methods: Quantitative RT-PCT was used to explore the expression of miR-613 in breast Cancer clinical samples and cell lines. MTT, colony formation assay, spheroid formation assay and xenograft tumor growth assay were used to investigate the role of miR-613 in vitro and in vivo. Cell Apoptosis and surface marker expression were measured by flow cytometry. Dual-luciferase reporter assay was used to explore the function of miR-613 in regulating FAM83A 3'UTR. Immunohistochemical staining was used to investigate the expression of FAM83A in TNBC tissues.

Results: We found that miR-613 expression was significantly downregulated in breast Cancer tissues and was even lower in TNBC compared with that in Other types of breast Cancer. A similar result was found in breast Cancer cell lines. Further analysis indicated that miR-613 could suppress TNBC cell growth, chemoresistance and stem-cell-like phenotype. Moreover, we also demonstrated that miR-613 suppressed tumorigenesis in vivo. Mechanically, we explored the downstream target of miR-613 and identified that miR-613 could directly bind to the 3'UTR of FAM83A, which contributed to the miR-613 mediated tumor suppression. The expression of miR-613 and FAM83A was negatively correlated. Restoring the expression of FAM83A attributed to the chemoresistance and stemness of TNBC cells.

Conclusion: We demonstrated that loss of miR-613 was critical for TNBC malignancy and restoring its expression could be served as a potential approach for TNBC treatment.

FAM83A; chemoresistance; miR-613; stemness; triple-negative breast cancer.