miR-126 suppresses epithelial-to-mesenchymal transition and metastasis by targeting PI3K/AKT/Snail signaling of lung cancer cells

摘要

Although previous studies have demonstrated that dysregulation of microRNA (miR)-126 is associated with the progression of several types of cancer, including lung cancer, the relationship between miR-126 and lung cancer metastasis remains unclear. SPC-A1 lung cancer cells were transfected with miR-126 mimic and negative control using Lipofectamine^® 3000. Following 2 h, TGF-β1 was used to induce epithelial-to-mesenchymal transition (EMT). The protein expression levels of EMT markers: E-cadherin, fibronectin, N-cadherin and vimentin were detected by western blot analysis or immunofluorescence staining. The results demonstrated that ectopic expression of miR-126 significantly suppresses the epithelial-to-mesenchymal transition process, which is considered to be the initial step of tumor metastasis, in SPC-A1 lung cancer cells. In addition, lentivirus-delivered miR-126 was demonstrated to endow Lewis lung carcinoma (LLC) cells with the ability to suppress lung metastasis in vivo. Previous studies have demonstrated that the molecular signals for this phenomenon involve the inhibition of the phosphoinositide 3-kinase/protein kinase B/Snail pathway by miR-126. The protein levels of p-PDK1 (S241) and p-AKT (S473) decreased in miR-126 mimic transfected SPC-A1 and LLC cells, compared with the control group, which were detected by western blot analysis. Reverse transcription-quantitative polymerase chain reaction and western blot analysis results indicated that the expression of Snail decreased in miR-126 mimic transfected SPC-A1 and LLC cells. In conclusion, these results revealed an important role for miR-126 in the regulation of the invasive and metastatic potential of lung cancer, and suggested a potential application for miR-126 in lung cancer treatment.