MicroRNA-1246 inhibits cell invasion and epithelial mesenchymal transition process by targeting CXCR4 in lung cancer cells.

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.