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MiR-876-5p suppresses epithelial–mesenchymal transition of lung cancer by directly down-regulating bone morphogenetic protein 4

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Abstract

Lung cancer is the leading cause of cancer-related death throughout the world. We aimed to investigate the role of a novel microRNA-876-5p and its potential molecular target bone morphogenetic protein 4 (BMP-4), in the epithelial–mesenchymal transition (EMT) of lung cancer. Expressions of microRNA-876-5p and its potential target BMP-4 were analysed in lung cancer cells and patient tissues. Luciferase activity assay was conducted to verify direct targeting of microRNA-876-5p to the 3′-UTR of BMP-4 mRNA. Migration, invasion capacities of lung cancer cells expressing microRNA-876-5p were analysed, and characteristics of lung cancer EMT protein markers were also evaluated. A xenograft tumour mouse model was established to address the roles of microRNA-876-5p and BMP-4 in lung cancer EMT in vivo. MicroRNA-876-5p was decreased while BMP-4 was increased in lung cancer cells and tissues. MicroRNA-876-5p directly targeted 3′-UTR of BMP-4 mRNA to inhibit its expression. MicroRNA-876-5p expression significantly inhibited the migration, invasion and EMT of lung cancer cells in vitro, as well as metastasis in vivo, which required BMP-4 expression. MicroRNA-876-5p suppresses EMT of lung cancer by directly down-regulating BMP-4, both of which could serve as potential therapeutic targets in the treatment of lung cancer.

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Authors and Affiliations

  1. Department of Respirology, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, 214002, Jiangsu Province, China

    Liang Bao, Lei Lv, Jinping Feng, Yuyu Chen, Xinhua Wang, Shuguang Han & Hongqing Zhao

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  1. Liang Bao
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  2. Lei Lv
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  3. Jinping Feng
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  4. Yuyu Chen
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  5. Xinhua Wang
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  6. Shuguang Han
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  7. Hongqing Zhao
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Corresponding author

Correspondence to Hongqing Zhao.

Additional information

Corresponding editor: Sorab N Dalal

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Supplementary figure 1

Expressions of other miRNAs predicted by miRanda algorithm to target BMP-4 mRNA in lung cancer cell lines. Expressions of miR-142, miR-340, miR-224, miR-18a and miR-18b, all of which were also predicted by miRanda algorithm to target BMP-4 mRNA, were examined in normal human lung epithelial cell line BEAS-2B and lung cancer cell lines A549 and HCC827. Data were shown as mean±SD from at least three independent experiments. ns not significant compared to BEAS-2B. (DOCX 96 kb)

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Bao, L., Lv, L., Feng, J. et al. MiR-876-5p suppresses epithelial–mesenchymal transition of lung cancer by directly down-regulating bone morphogenetic protein 4. J Biosci 42, 671–681 (2017). https://doi.org/10.1007/s12038-017-9722-5

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  • DOI: https://doi.org/10.1007/s12038-017-9722-5

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