The Transcription Factor SOX6 Regulates Autophagy Levels Through LAMP5 to Inhibit the Development of Pituitary Adenomas

Pituitary adenoma (PA) is a common type of brain tumor, and existing treatment options have limited efficacy in clinical settings. Autophagy is a risk factor for PA progression, and lysosome-associated membrane protein family member 5 (LAMP5) plays a regulatory role in tumor Autophagy. Therefore, this study aimed to investigate the role of LAMP5 in PA Autophagy, laying the foundation for the development of alternative therapies for PA. A tumor-bearing model was constructed by injecting rat pituitary tumor cells (GH3) into the left back of nude mice. RT‒qPCR, Western blotting, immunofluorescence, and immunohistochemistry were used to detect the expression of related genes and proteins. CCK-8, colony formation, and Transwell assays were employed to assess the malignant biological characteristics of the cells. Monodansylcadaverine (MDC) staining was used to detect autophagosome formation in cells. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter gene assays were conducted to validate the interaction between SOX6 and LAMP5. LAMP5 expression is upregulated in PAs and that LAMP5 knockdown inhibits GH3 cell proliferation, migration, and tumor tissue growth in nude mice. Additionally, Autophagy is activated in PAs, and LAMP5 knockdown suppresses GH3 cell Autophagy. Supplementation with the Autophagy activator rapamycin promotes the proliferation and migration of GH3 cells under LAMP5 knockdown conditions. Further research revealed that NF-κB is abnormally activated in PAs and that LAMP5 can activate Autophagy through NF-κB activation. Moreover, SOX6 expression is downregulated in PAs, and SOX6 is a negative transcriptional regulator of LAMP5. The overexpression of SOX6 inhibits GH3 cell Autophagy, proliferation, and migration, which can be reversed by LAMP5 overexpression or the NF-κB Activator PMA. Our study demonstrated that SOX6 can inhibit NF-κB-dependent Autophagy by suppressing LAMP5 expression, thereby restraining PA progression. LAMP5 may serve as a potential therapeutic target for PA.