Lili Han, Ruiyan Wang, Mengyu He, Zhenyue Chen, Feng Wang
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引用次数: 0
摘要
CSRP1（富含半胱氨酸和甘氨酸的蛋白 1）是一种经常在各种癌症中过度激活的蛋白，它能促进细胞增殖和存活，是癌症发展的一个关键因素。但值得注意的是，该蛋白对急性髓性白血病（AML）中糖酵解过程的影响尚未得到研究。本研究旨在探讨 METTL3/YTHDF1 轴在调节糖酵解过程中的作用及其通过稳定 CSRP1 mRNA 对 AML 进展的影响。我们使用定量实时 PCR（qRT-PCR）和 Western 印迹法分析了 CSRP1 在 AML 组织和细胞系中的表达。为了评估CSRP1敲除或过表达对AML细胞的影响，我们进行了包括细胞活力、集落形成、糖酵解相关指标在内的功能测试。为了阐明METTL3/YTHDF1介导的CSRP1 mRNA调控机制，还进行了RNA免疫沉淀（RIP）和RNA稳定性测定。CSRP1在AML组织和细胞系中明显上调。敲除CSRP1可抑制AML细胞增殖和糖酵解。过表达CSRP1可促进AML细胞存活。从机制上讲，METTL3通过m6A修饰增强了CSRP1 mRNA的稳定性，YTHDF1识别并结合CSRP1，阻止了mRNA的降解。METTL3/YTHDF1/CSRP1轴通过调节糖酵解在急性髓细胞性白血病的进展中发挥着关键作用。靶向这一途径可为急性髓细胞性白血病的治疗提供一种新的治疗策略。
METTL3/YTDHF1 Stabilizes CSRP1 mRNA to Regulate Glycolysis and Promote Acute Myeloid Leukemia Progression.
CSRP1 (Cysteine and Glycine-Rich Protein 1) is a protein often overactivated in various cancers, promoting cell proliferation and survival, making it a key factor in cancer development. However, it is worth noting that the effect of this protein on the glycolysis process in Acute Myeloid Leukemia (AML) has not yet been studied. This study aims to investigate the role of the METTL3/YTHDF1 axis in regulating Glycolysis and its impact on AML progression by stabilizing CSRP1 mRNA. We analyzed CSRP1 expression in AML tissues and cell lines using quantitative real-time PCR (qRT-PCR) and Western blotting. Functional assays, including cell viability, colony formation, glycolysis related indicators, were performed to assess the impact of CSRP1 knockdown or overexpression on AML cells. RNA immunoprecipitation (RIP) and RNA stability assays were conducted to elucidate the mechanism of METTL3/YTHDF1-mediated regulation of CSRP1 mRNA. CSRP1 was significantly upregulated in AML tissues and cell lines. Knockdown of CSRP1 inhibited AML cell proliferation and glycolysis. Overexpression of CSRP1 promoted AML cell survival. Mechanistically, METTL3 enhanced CSRP1 mRNA stability via m6A modification, recognized and bound by YTHDF1, preventing mRNA degradation. The METTL3/YTHDF1/ CSRP1 axis plays a critical role in AML progression by regulating glycolysis. Targeting this pathway may provide a novel therapeutic strategy for AML treatment.
期刊介绍：
Cell Biochemistry and Biophysics (CBB) aims to publish papers on the nature of the biochemical and biophysical mechanisms underlying the structure, control and function of cellular systems
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