HNRNPC稳定m6a修饰的AC145207.5，通过阻止Nrf2/GPX4轴介导的铁凋亡来加速结直肠癌的肿瘤发生

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research Pub Date : 2025-04-07 DOI:10.1016/j.ncrna.2025.04.002

Dan Liu , Shanshan Lin , Yueben Hu , Jianyong Xiong , Hongtao Wan , Yanglin Chen , Taohui Ding , Hu Zhao , Renjie Jiang , Zhijiang Huang , Dengke Yao , Ming Li , Xiaojian Zhu , Bo Yi

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引用次数: 0

摘要

铁凋亡是一种不依赖于细胞凋亡的细胞死亡途径，其特征是脂质过氧化升高，具有抑制肿瘤的前景。尽管对长链非编码rna （LncRNAs）在铁下垂中的作用进行了广泛的研究，但它们在结直肠癌（CRC）中的作用仍未得到充分探讨。我们通过公共数据集分析和内部验证研究了AC145207.5和HNRNPC在结直肠癌组织中的表达上调，确定它们具有重要的诊断潜力。体外实验包括MTS测定、transwell和集落形成，以及使用异种移植模型的体内研究，阐明了HNRNPC/AC145207.5轴在促进CRC恶性特征中的协同致癌作用。从机制上说，m6A读取器HNRNPC稳定了m6A修饰的AC145207.5，有助于其稳定和上调。因此，AC145207.5激活Nrf2/GPX4轴，导致GPX4表达增加，抑制GPX4介导的铁下垂，促进CRC进展。我们的研究结果强调了HNRNPC/AC145207.5轴在结直肠癌中的临床相关性，并阐明了其在铁下垂中的调节作用，为结直肠癌的靶向精准医学提供了指导。

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HNRNPC stabilizes m6A-modified AC145207.5 to accelerate tumorigenesis in colorectal cancer by impeding the Nrf2/GPX4 axis-mediated ferroptosis

Ferroptosis is an apoptosis-independent cell death pathway characterized by heightened lipid peroxidation, which shows promise for tumor suppression. Despite extensive research on long non-coding RNAs (LncRNAs) in ferroptosis, their role in colorectal cancer (CRC) remains underexplored. We investigated the upregulation of AC145207.5 and HNRNPC expression in CRC tissues through public dataset analysis and in-house validation, identifying them as having significant diagnostic potential. In vitro experiments including MTS assay, transwell, and colony formation, alongside in vivo studies using xenograft models, elucidated the synergistic carcinogenic role of the HNRNPC/AC145207.5 axis in promoting the malignant characteristics of CRC. Mechanistically, the m6A reader HNRNPC stabilized m6A-modified AC145207.5, contributing to its stabilization and upregulation. Consequently, AC145207.5 activated the Nrf2/GPX4 axis, resulting in increased GPX4 expression, inhibition of GPX4-mediated ferroptosis, and facilitation of CRC progression. Our findings underscore the clinical relevance of the HNRNPC/AC145207.5 axis in CRC and illuminate its regulatory role in ferroptosis, suggesting implications for targeted precision medicine in CRC.

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来源期刊

Non-coding RNA Research Medicine-Biochemistry (medical)

CiteScore

7.70

自引率

6.00%

发文量

审稿时长

49 days

期刊介绍： Non-coding RNA Research aims to publish high quality research and review articles on the mechanistic role of non-coding RNAs in all human diseases. This interdisciplinary journal will welcome research dealing with all aspects of non-coding RNAs-their biogenesis, regulation and role in disease progression. The focus of this journal will be to publish translational studies as well as well-designed basic studies with translational and clinical implications. The non-coding RNAs of particular interest will be microRNAs (miRNAs), small interfering RNAs (siRNAs), small nucleolar RNAs (snoRNAs), U-RNAs/small nuclear RNAs (snRNAs), exosomal/extracellular RNAs (exRNAs), Piwi-interacting RNAs (piRNAs) and long non-coding RNAs. Topics of interest will include, but not limited to: -Regulation of non-coding RNAs -Targets and regulatory functions of non-coding RNAs -Epigenetics and non-coding RNAs -Biological functions of non-coding RNAs -Non-coding RNAs as biomarkers -Non-coding RNA-based therapeutics -Prognostic value of non-coding RNAs -Pharmacological studies involving non-coding RNAs -Population based and epidemiological studies -Gene expression / proteomics / computational / pathway analysis-based studies on non-coding RNAs with functional validation -Novel strategies to manipulate non-coding RNAs expression and function -Clinical studies on evaluation of non-coding RNAs The journal will strive to disseminate cutting edge research, showcasing the ever-evolving importance of non-coding RNAs in modern day research and medicine.