GPX2 promotes the progression of lung adenocarcinoma metastasis by inhibiting the ferroptosis
ZHANG Tao,ZHANG Zhong-wei,WU Di
Tianjin Nankai Hospital, Tianjin (301000), China
Abstract:
Objective To investigate the effect and mechanism of glutathione peroxidase 2 (GPX2) on the progression of lung adenocarcinoma metastasis. Methods The TCGA database was used to analyze differentially expressed genes and ferroptosis regulatory genes in metastatic and primary lung adenocarcinoma (LUAD) tumors; GEPIA database was used the to analyze the expression of differentially expressed genes in LUAD cancer tissue and adjacent tissues, and analyze the role of GPX2 in the clinical prognosis of LUAD; The small interfering RNA transfection experiment was used to knock down the expression of GPX2 in A549 and PC-9 cell lines, RT-qRCR and Western blotting experiments were used to detect GPX2 expression, CCK-8 experiments were used to detect the relative cell viability of A549 and PC-9 cell lines, Transwell experiments were used to detect the invasiveness of A549 and PC-9 cell lines, and the kit was used to detect the GSH/GSSG ratio and ROS level in A549 and PC-9 cell lines. The relative viability and invasiveness of A549 and PC-9 cells were measured after Ferrostatin 1, an iron death inhibitor, was used to target the iron death process. Results The expression level of GPX2 in LUAD metastatic tumors was significantly higher than that in primary tumors, and the expression level in cancer was significantly higher than that in adjacent tissues. The high expression of GPX2 is closely related to the clinical stage and overall survival time of LUAD, indicating poor prognosis. Knocking down the expression level of GPX2 can significantly reduce the proliferation and invasion ability of A549 and PC-9 cell lines, significantly reduce the GSH/GSSG ratio, and significantly increase the ROS level. At the same time, the use of ferroptosis inhibitors can reverse the proliferation and invasion inhibition effect of knocking down GPX2 in A549 and PC-9 cell lines. Conclusion The increased expression of GPX2 is an important molecular change in the metastasis of lung adenocarcinoma. GPX2 promotes the proliferation and invasion of lung adenocarcinoma through ferroptosis inhibition, and it is expected to be a molecular marker for early prediction of lung adenocarcinoma metastasis.
