研究动态
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ANK1 通过促进铁死亡来抑制骨肉瘤的恶性进展。

ANK1 inhibits malignant progression of osteosarcoma by promoting ferroptosis.

发表日期:2024 Aug 31
作者: Fei Zhang, Junming Wan, Jinghua Zhong, Jianwen Mo
来源: Cell Death & Disease

摘要:

骨肉瘤(OS)是一种恶性程度高、预后差的原发性骨肿瘤。铁死亡在操作系统中起着至关重要的作用。本研究旨在评估锚蛋白1(ANK1)对OS的影响并探讨其具体机制。本研究选择与“骨肉瘤”相关的微阵列数据集。通过生物信息学分析确定了 OS 中的相关枢纽基因。转染的U-2OS和MG-63细胞用于体外实验。通过 CCK-8、伤口愈合和 Transwell 实验确定 ANK1 过表达对细胞活力、迁移和侵袭的影响。建立了 OS 小鼠模型用于体内实验。采用苏木精-伊红染色和免疫组化观察ANK1过表达对小鼠肿瘤的组织学影响。通过TUNEL染色评估小鼠细胞凋亡。GSE16088和GSE19276数据集中共有159个常见差异表达基因。鉴定出中心基因 ANK1、AHSP、GYPB、GYPA、KEL 和 ALAS2。泛癌分析证实ANK1与癌症预后和免疫浸润密切相关。此外,ANK1过表达抑制OS细胞的增殖、迁移和侵袭并促进铁死亡,而铁死亡抑制剂(fer-1)减弱了这些作用。此外,ANK1过表达可抑制肿瘤生长,促进细胞凋亡,减少体内Ki67阳性细胞数量,并增加体内caspase-3阳性细胞数量。ANK1是OS的预后生物标志物,可通过促进铁死亡来缓解OS的进展。 © 2024。作者。
Osteosarcoma (OS) is a primary bone tumor with high malignancy and poor prognosis. Ferroptosis plays a crucial role in OS. This study aimed to evaluate the effects of Ankyrin 1 (ANK1) on OS and to investigate its specific mechanisms.Microarray datasets related to "osteosarcoma" were selected for this study. Relevant hub genes in OS were identified through bioinformatics analysis. Transfected U-2OS and MG-63 cells were used for in vitro experiments. The effects of ANK1 overexpression on cell viability, migration, and invasion were determined through CCK-8, wound healing, and transwell assays. An OS mouse model was established for the in vivo experiments. Hematoxylin-eosin staining and immunohistochemistry were conducted to observe the histological effects of ANK1 overexpression on mouse tumors. TUNEL staining was performed to evaluate apoptosis in mouse.There were 159 common differentially expressed genes in the GSE16088 and GSE19276 datasets. The hub genes ANK1, AHSP, GYPB, GYPA, KEL, and ALAS2 were identified. Pan-cancer analysis verified that ANK1 was closely associated with cancer prognosis and immune infiltration. Furthermore, ANK1 overexpression inhibited the proliferation, migration, and invasion of OS cells and promoted ferroptosis, while ferroptosis inhibitor (fer-1) weakened these effects. Moreover, ANK1 overexpression suppressed tumor growth, promoted apoptosis, reduced the number of Ki67 positive cells, and elevated the number of caspase-3 positive cells in vivo.ANK1 is a prognosis biomarker of OS that can alleviate the progression of OS by promoting ferroptosis.© 2024. The Author(s).