AMBRA1 Inhibits Non-Small Cell Lung Cancer Progression Through miR-1178/p53/CDK2-Regulated Cell Cycle Arrest.

AMBRA1 is associated with a variety of pathological processes in cancer cells, but may have different functions in different tumour microenvironments or genetic backgrounds. In this study, the function and regulatory mechanisms of AMBRA1 were explored in the progression of non-small cell lung cancer (NSCLC). The abnormally expressed miRNAs in AMBRA1-overexpressed and differentially expressed genes in miR-1178-knockdown NSCLC cells were validated by RNA sequencing. Cell viability, proliferation, invasion, apoptosis, and cell cycle were tested through Cell Counting Kit-8 (CCK-8), EdU, colony formation, transwell, and flow cytometry. A mouse tumour xenograft model was conducted to assess the roles of the AMBRA1-miR-1178 axis on NSCLC progression in vivo. AMBRA1 overexpression suppressed NSCLC cell proliferation and invasion, while promoting apoptosis and G0/G1 phase cell cycle arrest in vitro, and inhibited tumour growth in vivo. RNA sequencing revealed miR-1178 as a target of AMBRA1. miR-1178 overexpression partially weakened the suppressive function of AMBRA1 on cell malignant biological behaviours. p53 and CDK2 were confirmed as the downstream targets of miR-1178. Silencing p53 or overexpressing CDK2 reversed the repressive effects of AMBRA1 on the development of NSCLC cells. AMBRA1 may suppress the malignant phenotype of NSCLC cells via regulating the miR-1178-p53-CDK2 signalling pathway.