Background: MicroRNA-876-5p (miR-876) dysregulation contributes to the aggressiveness of various types of human
cancer. This study was aimed at measuring miR-876 expression in
breast cancer, determining the specific roles of miR-876 in the progression of
breast cancer and understanding the corresponding molecular mechanisms. Materials and methods: miR-876 expression in
breast cancer tissues and cell lines was quantified via RT-qPCR. The effect of miR-876 upregulation on the malignant phenotype of
breast cancer cells was investigated using
CCK-8 assays, flow cytometry, Transwell migration and invasion assays and
tumor xenograft experiments. The mechanisms underlying the
tumor-suppressive action of miR-876 in
breast cancer cells were explored using bioinformatic analysis,
luciferase reporter assays, RT-qPCR and Western blot analysis. Results: miR-876 was found to be underexpressed in
breast cancer tissues and cell lines. Decreased miR-876 expression notably correlated with lymphatic invasion
metastasis, TNM stage and differentiation grade. Overall survival was lower among patients with
breast cancer and low miR-876 expression than in patients with high miR-876 expression. Restoration of miR-876 expression decreased
breast cancer cell proliferation, migration and invasion in vitro and restricted
tumor growth in vivo as well as increased cell apoptosis. Metadherin (MTDH) was identified as a novel target of miR-876 in
breast cancer cells. Furthermore, long intergenic nonprotein-coding
RNA 707 (LINC00707) acted as a molecular sponge for miR-876, thereby regulating MTDH expression in
breast cancer. Finally, silencing miR-876 expression attenuated the influence of a LINC00707 knockdown on the
malignancy of
breast cancer cells. Conclusion: This study, thus, revealed the vital functions of the LINC00707-miR-876-MTDH pathway in
breast cancer and provided attractive targets and markers for its treatment.