YY1-regulated AEBP1 drives the progression and inhibits ferroptosis of lung adenocarcinoma

Abstract

Abstract Lung adenocarcinoma (LUAD) is the most common and severe type of lung cancer and it is characterized by high morbidity and mortality rates. Adipocyte enhancer binding protein 1 (AEBP1), a cancer-promoting factor in several types of cancer, plays a significant regulatory role in cancer. However, the regulatory mechanism underlying the effect of AEBP1 on LUAD has not been previously investigated. Therefore, in the present study the mRNA and protein expression levels of AEBP1 were detected in LUAD cells by reverse transcription-quantitative PCR and western blot analysis, respectively. Furthermore, AEBP1 was silenced in LUAD cells using the cell transfection technology and Cell Counting Kit-8, EdU, clonogenesis, wound healing, Transwell and tube formation assays were performed to assess cell proliferation, invasion, migration and angiogenesis. Subsequently, thiobarbituric acid-reactive substances production rate and Fe2+ levels were measured using the corresponding kits. Reactive oxygen species levels were detected by BODIPY (581/591) C11 staining, while the effect of AEBP1 silencing on ferroptosis was evaluated via detecting the expression levels of ferroptosis-related proteins by western blot analysis. The association between AEBP1 and Yin Yang 1 (YY1) was verified by luciferase reporter gene and chromatin immunoprecipitation assays. To further uncover the regulatory mechanism of AEBP1, cells were simultaneously transfected with AEBP1 knockdown and YY1overexpression plasmids and the relevant indicators of cell proliferation, invasion, migration, angiogenesis and ferroptosis were assessed. The results showed that AEBP1 silencing inhibited the proliferation, metastasis and angiogenesis of LUAD cells. Additionally, AEBP1 knockdown induced ferroptosis in LUAD cells. The above regulatory effects of AEBP1 were triggered via regulating YY1 transcription factor. Overall, the current study suggested that YY1-regulated AEBP1 could promote the progression of LUAD and inhibit ferroptosis.