RAN Promotes Autophagy and Malignant Progression of Lung Adenocarcinoma through ATG101

This is the authors' abstract. We don't add key points for this paper.

This study investigates the role and mechanisms of Ras-related nuclear protein (RAN) in lung adenocarcinoma (LUAD). The expression of RAN in LUAD is studied using the The Cancer Genome Atlas (TCGA) database. Clinical samples are collected, and immunohistochemical (IHC) staining is performed to analyze the positive cell rate of RAN in normal and LUAD tissues. The study analyzes the effects of RAN overexpression in A549 and H1299 LUAD cell lines. Various methodologies are employed, including RT-PCR, Western blot, Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) staining, wound healing, Transwell assays, immunofluorescence, and 3,3'-ctetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining, to evaluate RAN's influence on cell proliferation, migration, and autophagy with mitochondrial homeostasis dysregulation. The findings reveal that RAN is significantly overexpressed in LUAD and associated with poorer prognosis. IHC analysis shows that the positive cell rate of RAN is significantly higher in LUAD tissues than in normal tissues. RAN overexpression facilitates proliferation and migration while enhancing autophagic activity, mitochondrial dysregulation, and increasing ATG101 expression. Suppression of ATG101 effectively counteracts the enhanced proliferation induced by RAN overexpression, highlighting ATG101 as a key mediator of RAN's effects. This study underscores the critical molecular dynamics of LUAD driven by RAN, suggesting that the RAN-ATG101 axis can serve as a novel therapeutic target.