Ursolic acid induces colorectal cancer cells ferroptosis via regulation of system xc- and miR-214-3p/Stat3/GPX4 axis

Background and aim: Colorectal cancer (CRC) is a prominent worldwide health concern because of its high prevalence and mortality rates. This study explored the role of Ursolic Acid (UA) in preventing the development of CRC and clarified potential mechanisms. Experimental procedure: Differential genes between human normal tissues and colon adenocarcinoma tumor tissues, plus survival analysis were generated on GEPIA2 website. RNA-seq was utilized to screen therapeutic targets after UA added into HT29 cells. AutoDock Vina 1.2.3 was used to carry out molecular docking between GPX4 and UA. Dual-luciferase reporter method was applied to evaluate miR-214-3p/GPX4 and miR-214-3p/Stat3 sponging. Gene overexpression plasmids, miRNA mimics and inhibitors transfection assays were carried out. The morphological alterations in mitochondria were detected based on transmission electron microscopy (TEM). In vivo, the xenograft model of HT29 cells transfected with luciferase gene (HT29-luc) was constructed in nude mice.