Table_1_GPX7 Is Targeted by miR-29b and GPX7 Knockdown Enhances Ferroptosis Induced by Erastin in Glioma.docx

BackgroundGlioma is a lethal primary tumor of central nervous system. Ferroptosis is a newly identified form of necrotic cell death. Triggering ferroptosis has shown potential to eliminate aggressive tumors. GPX7, a member of glutathione peroxidase family (GPXs), has been described to participate in oxidative stress and tumorigenesis. However, the biological functions of GPX7 in glioma are still unknown.MethodsBioinformatics method was used to assess the prognostic role of GPX7 in glioma. CCK8, wound healing, transwell and cell apoptosis assays were performed to explore the functions of GPX7 in glioma cells. In vivo experiment was also conducted to confirm in vitro findings. Ferroptosis-related assays were carried out to investigate the association between GPX7 and ferroptosis in glioma.ResultsGPX7 was aberrantly expressed in glioma and higher expression of GPX7 was correlated with adverse outcomes. GPX7 silencing enhanced ferroptosis-related oxidative stress in glioma cells and the loss of GXP7 sensitized glioma to ferroptosis induced by erastin. Furthermore, we found that miR-29b directly suppressed GPX7 expression post-transcriptionally. Reconstitution of miR-29b enhanced erastin sensitivity, partly via GPX7 suppression.ConclusionsOur study clarified the prognostic role of GPX7 in glioma and preliminarily revealed the role of GPX7 in ferroptosis, which may be conducive to the exploration of therapeutic targets of glioma.

背景：胶质瘤是一种致命的脑部原发肿瘤。铁死亡是一种新型的细胞坏死形式。触发铁死亡已被证明具有消除侵袭性肿瘤的潜力。GPX7，作为谷胱甘肽过氧化物酶家族（GPXs）的成员，已被描述为参与氧化应激和肿瘤发生。然而，GPX7在胶质瘤中的生物学功能尚不明确。方法：本研究采用生物信息学方法评估了GPX7在胶质瘤中的预后作用。通过CCK8、伤口愈合、Transwell和细胞凋亡实验探究了GPX7在胶质瘤细胞中的功能。此外，还进行了体内实验以验证体外结果。通过铁死亡相关实验研究了GPX7与胶质瘤中铁死亡之间的关联。结果：GPX7在胶质瘤中异常表达，且GPX7的高表达与不良预后相关。GPX7的沉默增强了胶质瘤细胞中铁死亡相关的氧化应激，而GXP7的丢失使得胶质瘤对erastin诱导的铁死亡更为敏感。此外，我们发现miR-29b可通过转录后途径直接抑制GPX7的表达。miR-29b的重组增强了erastin的敏感性，部分是通过抑制GPX7实现的。结论：本研究阐明了GPX7在胶质瘤中的预后作用，并初步揭示了GPX7在铁死亡中的作用，这有助于探索胶质瘤的治疗靶点。