MicroRNA-876 is sponged by long noncoding RNA LINC00707 and directly targets metadherin to inhibit breast cancer malignancy
Tong Li,1 Yunpeng Li,2 Hongyan Sun11Department 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 R...
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doaj-9c3e2a7b78f0453aaa1ba79a6fb3b4062020-11-25T01:56:15ZengDove Medical PressCancer Management and Research1179-13222019-06-01Volume 115255526946320MicroRNA-876 is sponged by long noncoding RNA LINC00707 and directly targets metadherin to inhibit breast cancer malignancyLi TLi YSun HTong Li,1 Yunpeng Li,2 Hongyan Sun11Department 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 ChinaBackground: 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 targethttps://www.dovepress.com/microrna-876-is-sponged-by-long-noncoding-rna-linc00707-and-directly-t-peer-reviewed-article-CMARbreast cancermicroRNA-876-5pmetadherinlong intergenic non-protein-coding RNA 707therapeutic target |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Li T Li Y Sun H |
spellingShingle |
Li T Li Y Sun H MicroRNA-876 is sponged by long noncoding RNA LINC00707 and directly targets metadherin to inhibit breast cancer malignancy Cancer Management and Research breast cancer microRNA-876-5p metadherin long intergenic non-protein-coding RNA 707 therapeutic target |
author_facet |
Li T Li Y Sun H |
author_sort |
Li T |
title |
MicroRNA-876 is sponged by long noncoding RNA LINC00707 and directly targets metadherin to inhibit breast cancer malignancy |
title_short |
MicroRNA-876 is sponged by long noncoding RNA LINC00707 and directly targets metadherin to inhibit breast cancer malignancy |
title_full |
MicroRNA-876 is sponged by long noncoding RNA LINC00707 and directly targets metadherin to inhibit breast cancer malignancy |
title_fullStr |
MicroRNA-876 is sponged by long noncoding RNA LINC00707 and directly targets metadherin to inhibit breast cancer malignancy |
title_full_unstemmed |
MicroRNA-876 is sponged by long noncoding RNA LINC00707 and directly targets metadherin to inhibit breast cancer malignancy |
title_sort |
microrna-876 is sponged by long noncoding rna linc00707 and directly targets metadherin to inhibit breast cancer malignancy |
publisher |
Dove Medical Press |
series |
Cancer Management and Research |
issn |
1179-1322 |
publishDate |
2019-06-01 |
description |
Tong Li,1 Yunpeng Li,2 Hongyan Sun11Department 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 ChinaBackground: 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 |
topic |
breast cancer microRNA-876-5p metadherin long intergenic non-protein-coding RNA 707 therapeutic target |
url |
https://www.dovepress.com/microrna-876-is-sponged-by-long-noncoding-rna-linc00707-and-directly-t-peer-reviewed-article-CMAR |
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