Abstract
Autophagy is essential for cellular metabolism and plays pivotal roles in carcinogenesis, while excessive autophagy induces toxicity and cell death. Our previous studies have suggested that let-7a-5p/BCL-xL might regulate autophagy in lung cancer, but the regulatory mechanism is unclear. The central goal of the study was to figure out the role of let-7a-5p/BCL-xL in the initiation of autophagy and its effect on the migration, invasion, and proliferation of A549 cells as well as its therapeutic potential in lung cancer. Based on the genome-wide expression profiles of lung cancer, BCL-xL and let-7a-5p were found to be dysregulated and negatively correlated in lung adenocarcinoma, which was associated with the survival of lung cancer. The crosstalk between BCL-xL and let-7a-5p was then investigated using dual-luciferase reporter assay, and it was found to suppress the migration and invasion of A549 cells. Further, we found that the crosstalk between BCL-xL and let-7a-5p could lead to toxic autophagy and cell death through activating the PI3K-signaling pathway, which was independent of apoptosis or pyroptosis. These findings indicate that let-7a-5p is a sensitive initiator for toxic autophagy in A549 lung cancer cells and is an appealing target for lung cancer therapy.