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

Abstract

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 <i>in vivo</i>. 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.