胶质瘤
GPX4
癌症研究
下调和上调
细胞生物学
生物
蛋白质表达
化学
生物化学
基因
酶
谷胱甘肽
谷胱甘肽过氧化物酶
作者
Limei Deng,Y. Peter Di,Caiyun Chen,Juan Xia,Bingxi Lei,Ning Li,Qingyu Zhang
标识
DOI:10.1038/s41419-024-06486-z
摘要
Abstract Emerging evidence highlights the multifaceted contributions of m6A modifications to glioma. IGF2BP3, a m6A modification reader protein, plays a crucial role in post-transcriptional gene regulation. Though several studies have identified IGF2BP3 as a poor prognostic marker in glioma, the underlying mechanism remains unclear. In this study, we demonstrated that IGF2BP3 knockdown is detrimental to cell growth and survival in glioma cells. Notably, we discovered that IGF2BP3 regulated ferroptosis by modulating the protein expression level of GPX4 through direct binding to a specific motif on GPX4 mRNA. Strikingly, the m6A modification at this motif was found to be critical for GPX4 mRNA stability and translation. Furthermore, IGF2BP3 knockdown glioma cells were incapable of forming tumors in a mouse xenograft model and were more susceptible to phagocytosis by microglia. Our findings shed light on an unrecognized regulatory function of IGF2BP3 in ferroptosis. The identification of a critical m6A site within the GPX4 transcript elucidates the significance of post-transcriptional control in ferroptosis.
科研通智能强力驱动
Strongly Powered by AbleSci AI