Silencing circ FADS2 induces ferroptosis in colorectal cancer cells through miR - 152 - 3p / SLC7A11 signaling axis

Acta Universitatis Medicinalis Anhui 2025, 06, v.60 1000-1008     font:big middle small

Found programs: Hunan Province Socialized Funding Projects for Science and Technology Innovation Plan(No.2020SKC2009);Natural Science Foundation of Hunan Province(No.2024JJ7461);General Guidance Project of Hubei Provincial Health Commission(No.D202303038378);Guiding Plan Project of Science and Technology Bureau of Hengyang(No.202222035832)

Authors:Jiang Liangjun; Lu Xianzhou

Keywords:circFADS2; colorectal cancer; SW480 cells;death of iron; miR-152-3p; solute carrier family 7 member 11;

DOI:10.19405/j.cnki.issn1000-1492.2025.06.004

〔Abstract〕 Objective To investigate the effect and mechanism of silencing circFADS2 on ferroptosis in colorectal cancer(CRC) cells. Methods The human colon adenocarcinoma cell line SW480 was used as the research object. circFADS2 siRNA interference plasmid(si-circFADS2) and its negative control si-NC, miR-152-3p inhibitor and its negative control inhibitor-NC, miR-152-3p mimics and its negative control mimics NC, SLC7A11 overexpression plasmid(oe-SLC7A11) and its negative control vector were transfected into SW480 cells. Methylthiazolyldiphenyl-tetrazolium bromide(MTT) method was used to detect cell proliferation activity; The contents of ferrous ion(Fe2+), malondialdehyde(MDA) and the activities of superoxide dismutase(SOD) and glutathione(GSH) in cells were detected by chemical method. Dichlorodihydrofluorescein diacetate(DCFH-DA) probe was used to detect the level of reactive oxygen species(ROS) in cells. Quantitative Real-time polymerase chain reaction(qPCR) was used to detect the expression levels of miR-152-3p and SLC7A11 mRNA in cells. Western blot was used to detect the expression levels of ferroptosis-related proteins such as SLC7A11 and GPX4 in cells. Dual luciferase reporter gene experiment was used to verify the sponge adsorption relationship between miR-152-3p and circFADS2, and the targeted regulation relationship between miR-152-3p and SLC7A11. Results Compared with blank group, the proliferation activity of si-circFADS2 group decreased, the levels of Fe2+, MDA and ROS increased, and the levels of SOD and GSH decreased; At the same time, the expression level of miR-152-3p increased, and the protein expression levels of SLC7A11 and GPX4 decreased in cells(all P2+, MDA and ROS in cells decreased, and the levels of SOD and GSH increased; At the same time, the expression level of miR-152-3p decreased, and the protein expression levels of SLC7A11 and GPX4 increased(all P