LncRNA BBOX1-AS1 silencing inhibits esophageal squamous cell cancer progression by promoting ferroptosis via miR-513a-3p/SLC7A11 axis

Abstract

Long noncoding RNA BBOX1 antisense 1 (BBOX1-AS1) has been demonstrated to play important roles in several tumors. However, the expression and function of BBOX1-AS1 in esophageal squamous cell cancer (ESCC) have not been defined. Here, BBOX1-AS1 expression in 78 collected ESCC tissues, paired adjacent normal tissues, and ESCC cell lines were analyzed using quantitative real-time polymerase chain reaction. The overall survival of the patients was also studied. Cell proliferation, invasion, and migration were verified by constructing in vitro models. Additionally, cell apoptosis was determined by flow cytometry, and ferroptosis was examined using Ptgs2 detection and lipid-reactive oxygen species assays. The relationship between BBOX1-AS1 and downstream molecules was evaluated using RNA immunoprecipitation, western blotting, and luciferase reporter assays. The function of BBOX1-AS1 was studied in vivo using a xenograft model and immunohistochemistry. BBOX1-AS1 expression was significantly higher in ESCC tissues, indicating poor prognosis. Inhibition of BBOX1-AS1 reduced cell proliferation, slowed cell invasion and migration, and promoted apoptosis and ferroptosis in vitro. miR-513a-3p was verified as a specific target of BBOX1-AS1 in ESCC, whereas knockdown of miR-513a-3p reversed the suppressive function of BBOX1-AS1 silencing in TE-1 cells. Moreover, solute carrier family 7 member 11 (SLC7A11) is regulated by miR-513a-3p, which is mediated by BBOX1-AS1 in ESCC cells. In conclusion, downregulation of BBOX1-AS1 inhibits cell proliferation, and metastasis accelerates cell apoptosis and ferroptosis in ESCC by upregulating miR-513a-3p to reduce SLC7A11 expression. These findings may provide novel insights into the diagnosis and treatment of ESCC.