MicroRNA-876 is sponged by long noncoding RNA LINC00707 and directly targets metadherin to inhibit breast cancer malignancy

Cancer Manag Res. 2019 Jun 6:11:5255-5269. doi: 10.2147/CMAR.S210845. eCollection 2019.


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.

Keywords: breast cancer; long intergenic non-protein-coding RNA 707; metadherin; microRNA-876-5p; therapeutic target.

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  • Retracted Publication