MicroRNAs (miRNAs) have been regarded as important regulators in different pathological processes of cells. Abnormal expression of miRNAs is frequently associated with cell proliferation, metastasis and apoptosis in various cancers. This study aimed to explore the effect of miR-146-5p on cell growth, metastasis and its mechanism in lung cancer cells. The expressions of miR-146-5p and claudin-12 in A549 and WI-38 cells were altered by transient transfection. Cisplatin was used to develop cells for regulation of cisplatin sensitivity. Cell viability, migration, invasion, and apoptosis were analyzed by CCK-8, Transwell and flow cytometry assays. The protein expressions of Wnt/β-catenin and PI3K/AKT/MAPK pathway-related factors were detected. miR-146-5p suppression inhibited cell viability, migration and invasion but promoted apoptosis in A549 cells. Moreover, overexpression of miR-146-5p reduced the sensitivity of A549 cells and WI-38 cells to cisplatin. In addition, claudin-12 was a direct target of miR-146-5p and was negatively regulated by miR-146-5p. Claudin-12 silence significantly reversed miR-146-5p suppression-mediated anti-tumor effects in A549 cells. Furthermore, miR-146-5p overexpression activated Wnt/β-catenin and PI3K/AKT/MAPK signal pathways via down-regulation of claudin-12. The results indicated that miR-146-5p promoted cell viability, migration and invasion, inhibited apoptosis and activated Wnt/β-catenin and PI3K/AKT/MAPK signal pathways by regulating claudin-12 expression in lung cancer cells.
Keywords: PI3K/AKT/MAPK signaling pathways; cisplatin; claudin-12; lung cancer; miR-146-5p; wnt/β-catenin.