FAM20C Modulates Neuronal Differentiation in Hypoxic-Ischemic Brain Damage via KAP1 Phosphorylation and LINE1 RNA m6A-Dependent H3K9me3 Regulation.

IF 5.6 1区生物学 Q2 CELL BIOLOGY

Cell Proliferation Pub Date : 2025-06-13 DOI:10.1111/cpr.70073

Chen-Xi Feng, Mei Wang, Gen Li, Si-Jia Chu, Di Wu, Xiao-Han Hu, Li-Xiao Xu, Mei Li, Xing Feng

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引用次数: 0

Abstract

Neurodevelopmental impairment due to hypoxic-ischemic brain damage (HIBD) lacks effective biomarkers and therapeutic targets. Based on some cues from published papers, extracellular serine/threonine protein kinase FAM20C was speculated to play a crucial role in the neurodevelopmental impairment of HIBD. In this study, FAM20C was found suppressed in the ischemic hippocampal tissue of HIBD. The inhibition of FAM20C caused by HIBD affected cell differentiation and subsequently caused cognitive impairment. KAP1 was identified as a kinase substrate of FAM20C in the central nervous system. The regulation of the YTHDC1-NCL-KAP1-LINE1 RNA complex by FAM20C was mediated through KAP1 phosphorylation and LINE1 RNA m6A. These alterations consequently modulated the establishment of the H3K9me3 modification on LINE1 DNA, thereby resulting in neuronal differentiation. Furthermore, E2F4, identified as a transcription factor, regulated FAM20C in HIBD. This research has clarified the novel association between FAM20C and HIBD, laying the foundation for innovative diagnostic and therapeutic strategies to counteract neurodevelopmental disruptions arising from neonatal hypoxic-ischemic encephalopathy (HIE).

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FAM20C通过KAP1磷酸化和LINE1 RNA m6a依赖性H3K9me3调控调控缺氧缺血性脑损伤的神经元分化

缺氧缺血性脑损伤（HIBD）导致的神经发育障碍缺乏有效的生物标志物和治疗靶点。根据一些已发表论文的线索，推测细胞外丝氨酸/苏氨酸蛋白激酶FAM20C在HIBD的神经发育障碍中起关键作用。本研究发现FAM20C在HIBD缺血海马组织中被抑制。HIBD对FAM20C的抑制影响细胞分化，进而导致认知障碍。KAP1被鉴定为FAM20C在中枢神经系统中的激酶底物。FAM20C通过KAP1磷酸化和LINE1 RNA m6A介导YTHDC1-NCL-KAP1-LINE1 RNA复合物的调控。这些改变调节了LINE1 DNA上H3K9me3修饰的建立，从而导致神经元分化。此外，E2F4作为一种转录因子，在HIBD中调控FAM20C。本研究阐明了FAM20C与HIBD之间的新关联，为创新诊断和治疗策略以对抗新生儿缺氧缺血性脑病（HIE）引起的神经发育中断奠定了基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Proliferation 生物-细胞生物学

CiteScore

14.80

自引率

2.40%

发文量

198

审稿时长

1 months

期刊介绍： Cell Proliferation Focus: Devoted to studies into all aspects of cell proliferation and differentiation. Covers normal and abnormal states. Explores control systems and mechanisms at various levels: inter- and intracellular, molecular, and genetic. Investigates modification by and interactions with chemical and physical agents. Includes mathematical modeling and the development of new techniques. Publication Content: Original research papers Invited review articles Book reviews Letters commenting on previously published papers and/or topics of general interest By organizing the information in this manner, readers can quickly grasp the scope, focus, and publication content of Cell Proliferation.