Liu Hongjun, Tan Shasha, Zhao Zhenyu, Tang Xiaoping, Li Zhou, Qi Jian
Department of Neurosurgery, The Affiliated Hospital of North Sichuan Medical College, 637000 Nanchong, Sichuan, China.
Department of Neurosurgery, The Affiliated Nanchong Central Hospital of North Sichuan Medical College, 637000 Nanchong, Sichuan, China.
Front Biosci (Landmark Ed). 2025 Feb 14;30(2):25718. doi: 10.31083/FBL25718.
Gliomas are aggressive brain tumors known for their poor prognosis and resistance to standard treatment options. Ferroptosis is an iron-dependent form of regulated cell death that has emerged as a promising target for cancer treatment. This study examined how the methyltransferase-like 3/YTH domain family protein 1 () axis influences ferroptosis and glioma progression by stabilizing mitochondrial carrier homolog 2 () messenger RNA (mRNA).
expression in glioma tissues and cell lines was evaluated through quantitative real-time polymerase chain reaction (PCR) and western blot analyses. To assess the effects of knockdown and overexpression on glioma cell functions, we performed a series of functional assays, including cell viability, colony formation, and measurements of lipid reactive oxygen species (lipid ROS) and malondialdehyde (MDA) levels. Additionally, we conducted RNA immunoprecipitation (RIP) and RNA stability assays to explore the underlying mechanisms governing the interaction between , , and the stability of mRNA.
was significantly upregulated in glioma tissues and cell lines. Silencing of resulted in decreased glioma cell proliferation and induced ferroptosis, as evidenced by increased lipid peroxidation and ROS accumulation. Conversely, overexpression of enhanced glioma cell survival and reduced ferroptosis. -mediated N6-methyladenosine (m6A) modification enhanced mRNA stability by enabling YTHDF1 to bind and protect the modified mRNA from degradation.
The axis plays a critical role in glioma progression by inhibiting ferroptosis and promoting tumor cell survival. Targeting this pathway may provide a new and effective treatment strategy for glioma patients.
胶质瘤是侵袭性脑肿瘤，预后较差且对标准治疗方案耐药。铁死亡是一种铁依赖性的程序性细胞死亡形式，已成为癌症治疗的一个有前景的靶点。本研究探讨了甲基转移酶样3/YTH结构域家族蛋白1（ ）轴如何通过稳定线粒体载体同源物2（ ）信使核糖核酸（mRNA）来影响铁死亡和胶质瘤进展。
通过定量实时聚合酶链反应（PCR）和蛋白质免疫印迹分析评估 在胶质瘤组织和细胞系中的表达。为评估敲低和过表达 对胶质瘤细胞功能的影响，我们进行了一系列功能试验，包括细胞活力、集落形成以及脂质活性氧（脂质ROS）和丙二醛（MDA）水平的测定。此外，我们进行了RNA免疫沉淀（RIP）和RNA稳定性试验，以探索 、 之间相互作用以及 mRNA稳定性的潜在机制。
在胶质瘤组织和细胞系中显著上调。敲低 导致胶质瘤细胞增殖减少并诱导铁死亡，脂质过氧化增加和ROS积累证明了这一点。相反， 过表达增强了胶质瘤细胞存活并减少了铁死亡。 介导的N6-甲基腺苷（m6A）修饰通过使YTHDF1结合并保护修饰后的mRNA不被降解来增强 mRNA稳定性。
轴通过抑制铁死亡和促进肿瘤细胞存活在胶质瘤进展中起关键作用。靶向该途径可能为胶质瘤患者提供一种新的有效治疗策略。
