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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MicroRNA-1246 inhibits cell invasion and epithelial mesenchymal transition process by targeting CXCR4 in lung cancer
Background:
Recent studies have indicated that microRNAs (miRNAs) are closely related to lung cancer. However, the effects of miR-1246 on lung cancer are still elusive. In this study, we aimed to explore the molecular mechanisms of miR-1246 in lung cancer.
Materials And Methods:
Using RT-qPCR assay, we analyzed the expression of miR-1246 in lung cancer cell lines and lung epithelial cell line. Using Cell Counting Kit-8 (CCK-8), flow cytometry, Transwell, RT-qPCR and western blot assays, we investigated cell viability, apoptosis, invasion and epithelial mesenchymal transition (EMT) process. Using luciferase reporter assay, we confirmed a target of miR-1246. Using western blot assay, we detected the protein mechanisms of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signal pathways.
Results:
Our results showed that miR-1246 was down-regulated in lung cancer cell lines (A549, H1650 and H1299) compared to in lung epithelial cell line (16HBE14o). MiR-1246 overexpression remarkably inhibited cell invasion as well as up-regulated E-cadherin expression and down-regulated N-cadherin, Vimentin, ZEB1 and Snail expressions in A549 cells. Further studies have confirmed CXCR4 as a target gene of miR-1246, and CXCR4 silence significantly abolished the promotion effect of miR-1246 suppression on cell invasion and EMT process in A549 cells. Besides, miR-1246 blocked JAK/STAT and PI3K/AKT signal pathways by regulation of CXCR4.
Conclusions:
These results demonstrated that miR-1246 inhibited cell invasion and EMT process by targeting CXCR4 and blocking JAK/STAT and PI3K/AKT signal pathways in lung cancer cells.
Insights
MicroRNA-1246 (miR-1246) is downregulated in lung cancer. Overexpression of miR-1246 inhibits cancer cell invasion and epithelial-mesenchymal transition by targeting CXCR4 and blocking key signaling pathways.
Area of Science:
- Molecular Oncology
- Cell Biology
- Cancer Research
Background:
- MicroRNAs (miRNAs) play a role in lung cancer development.
- The specific function of miR-1246 in lung cancer remains unclear.
Purpose of the Study:
- To investigate the molecular mechanisms of miR-1246 in lung cancer.
- To explore the role of miR-1246 in lung cancer cell invasion and epithelial-mesenchymal transition (EMT).
Main Methods:
- RT-qPCR to analyze miR-1246 expression in lung cancer cell lines.
- Cell Counting Kit-8 (CCK-8), flow cytometry, and Transwell assays to assess cell viability, apoptosis, and invasion.
- Luciferase reporter assay to identify miR-1246 targets.
- Western blot to examine the JAK/STAT and PI3K/AKT signaling pathways.
Main Results:
- miR-1246 expression was significantly downregulated in lung cancer cell lines.
- Overexpression of miR-1246 inhibited cell invasion and EMT markers (N-cadherin, Vimentin, ZEB1, Snail) while upregulating E-cadherin.
- CXCR4 was identified as a direct target of miR-1246.
- miR-1246 suppressed the JAK/STAT and PI3K/AKT signaling pathways via CXCR4 regulation.
Conclusions:
- miR-1246 acts as a tumor suppressor in lung cancer.
- miR-1246 inhibits lung cancer cell invasion and EMT by targeting CXCR4.
- miR-1246 exerts its effects by modulating the JAK/STAT and PI3K/AKT signaling pathways.
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