Objective To investigate the effects of microRNA-429(miR-429)on the invasion,migration,and ferroptosis of lung adenocarcinoma(LUAD)cells,and to provide new insights into the clinical inhibition of LUAD invasion and migration and the promotion of ferroptosis.Methods The expression profile of miR-429 in LUAD tissues was analyzed using the starBase database.Quantitative real-time PCR(qRT-PCR)was performed to assess miR-429 expression levels in normal human bronchial epithelial cells(the BEAS-2B cell line)and LUAD cells(the A549 and H1975 cell lines),and to evaluate the plasmid transfection efficiency.The effects of miR-429 on A549 cell proliferation,migration,and invasion were assessed using 5-ethynyl-2'-deoxyuridine(EdU)incorporation assay,scratch wound healing assay,and Transwell invasion assay,respectively.Potential ferroptosis-related proteins targeted by miR-429 were predicted using bioinformatics databases,and the targeting relationship between miR-429 and heme oxygenase 1(HMOX1)was validated by a dual-luciferase reporter assay.Further functional experiments were performed to examine the effect of miR-429 targeting HMOX1 on the malignant phenotypes of A549 cells.The levels of reactive oxygen species(ROS)and lipid ROS(L-ROS)were measured to analyze the regulatory effects of miR-429 and HMOX1 on oxidative stress in LUAD cells.The contents of malondialdehyde(MDA),glutathione(GSH),and ferrous ion(Fe2+)were measured to evaluate evaluate the effects of miR-429 and HMOX1 on key ferroptosis-associated indicators in LUAD cells.Results miR-429 expression was significantly higher in LUAD cell lines(A549 and H1975)compared with that in normal cells(BEAS-2B),with the highest expression level observed in A549 cells.Functional experiments demonstrated that miR-429 promoted A549 cell proliferation,migration,and invasion.The dual-luciferase assay confirmed that miR-429 directly targeted HMOX1,and their expression levels were negatively correlated in LUAD cells.HMOX1 overexpression inhibited the proliferation,invasion,and migration of A549 cells,while miR-429 overexpression reversed these inhibitory effects.Mechanistically,miR-429 targeted and inhibited HMOX1,which led to reduced intracellular levels of ROS,L-ROS,MDA,and Fe2+and increased GSH levels in A549 cells,thereby decreasing cellular sensitivity to ferroptosis.Conclusion miR-429 promotes the invasion and migration of LUAD cells and inhibits ferroptosis by targeting and inhibiting HMOX1.
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