MicroRNA-876 is sponged by long noncoding RNA LINC00707 and directly targets metadherin to inhibit breast cancer malignancy
Authors Li T, Li Y, Sun H
Received 1 April 2019
Accepted for publication 6 May 2019
Published 6 June 2019 Volume 2019:11 Pages 5255—5269
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Antonella D'Anneo
Tong Li,1 Yunpeng Li,2 Hongyan Sun1
1Department of General Surgery, The Fourth People’s Hospital of Jinan, Jinan, Shandong 250031, People’s Republic of China; 2Department of General Surgery, Ningjin County People’s Hospital, Ningjin, Shandong 253400, People’s Republic of China
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, microRNA-876-5p, metadherin, long intergenic non-protein-coding RNA 707, therapeutic target
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