TFAP2A Promotes Cell Progression and Suppresses Ferroptosis in Lung Adenocarcinoma via Activating Transcription of CST1

Abstract

Lung adenocarcinoma (LUAD) is a common type of lung cancer with complicated pathological mechanism. Transcription Factor AP-2 Alpha (TFAP2A) and Cysteine protease inhibitor 1 (CST1) are upregulated genes in LUAD samples, accordingly, we focused on clarifying the role of TFAP2A/CST1 axis in LUAD. Expression analysis was performed using real-time quantitative polymerase chain reaction and western blot. Cellular behaviors were detected by colony formation assay, EdU assay, wound healing assay and flow cytometry. Ferroptosis was assessed by oxidative indicators, Fe²⁺ level and related proteins. TFAP2A and CST1 interaction was analyzed via ChIP assay and dual-luciferase reporter assay. TFAP2A function in vivo was evaluated by xenograft tumor assay. CST1 was overexpressed in LUAD samples and cells. Downregulation of CST1 inhibited proliferation, migration but it promoted apoptosis and ferroptosis of LUAD cells. TFAP2A interacted with the promoter of CST1 to up-regulate CST1 expression. TFAP2A regulated the malignant behaviors and ferroptosis of LUAD cells by targeting CST1. TFAP2A affected LUAD tumor growth via mediating CST1. All these data proved that TFAP2A/CST1 axis contributed to proliferation, migration while it suppressed apoptosis and ferroptosis in LUAD.