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MiR-876-5p suppresses epithelial-mesenchymal transition of lung cancer by directly down-regulating bone morphogenetic
Liang Bao1, Lei Lv, Jinping Feng
1Department of Respirology, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi 214002, Jiangsu Province, China.
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.
Insights
MicroRNA-876-5p suppresses lung cancer progression by targeting bone morphogenetic protein 4 (BMP-4). Lower microRNA-876-5p and higher BMP-4 levels correlate with increased cancer cell migration, invasion, and metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Lung cancer is a leading cause of cancer mortality worldwide.
- Epithelial-mesenchymal transition (EMT) is a critical process in lung cancer progression and metastasis.
- MicroRNAs play crucial roles in regulating gene expression and cellular processes.
Purpose of the Study:
- To investigate the role of microRNA-876-5p and its target bone morphogenetic protein 4 (BMP-4) in lung cancer EMT.
- To determine the molecular mechanism by which microRNA-876-5p affects lung cancer cell behavior.
- To explore the therapeutic potential of microRNA-876-5p and BMP-4 in lung cancer treatment.
Main Methods:
- Analysis of microRNA-876-5p and BMP-4 expression in lung cancer cells and tissues.
- Luciferase activity assay to confirm direct targeting of BMP-4 mRNA by microRNA-876-5p.
- In vitro assays for cell migration, invasion, and EMT markers.
- In vivo xenograft mouse model to assess the role of microRNA-876-5p and BMP-4 in metastasis.
Main Results:
- MicroRNA-876-5p expression was decreased, while BMP-4 expression was increased in lung cancer.
- MicroRNA-876-5p directly targets and inhibits BMP-4 mRNA expression.
- MicroRNA-876-5p suppressed lung cancer cell migration, invasion, and EMT in vitro.
- MicroRNA-876-5p inhibited lung cancer metastasis in vivo, dependent on BMP-4 expression.
Conclusions:
- MicroRNA-876-5p acts as a tumor suppressor in lung cancer by down-regulating BMP-4.
- The microRNA-876-5p/BMP-4 axis is a key regulator of EMT and metastasis in lung cancer.
- MicroRNA-876-5p and BMP-4 represent potential therapeutic targets for lung cancer treatment.
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