Redox regulator LanCL1 suppresses glioma progression by coordinately inhibiting cell growth and regulating mitochondrial metabolism

IF 8.2 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Free Radical Biology and Medicine Pub Date : 2025-08-29 DOI:10.1016/j.freeradbiomed.2025.08.059

Yunbo Yuan , Junhong Li , Mengping Wang , Qiuyun Yuan , Yanhui Liu , Wanchun Yang , Mina Chen

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Abstract

Gliomas are highly aggressive and heterogeneous brain tumors with poor clinical outcomes, necessitating an urgent need for novel prognostic biomarkers and therapeutic targets. Redox regulation, which balances reactive oxygen species (ROS) generation with antioxidant defense mechanisms, has emerged as a crucial adaptive mechanism supporting glioma progression. However, the precise roles and clinical implications of redox-associated genes in glioma remain poorly defined. Here, we employed integrative analyses to explore the functional impact of redox-related genes in glioma and identified LanCL1 as a key regulator in glioma malignancy. Consensus clustering of 97 redox-related genes stratified gliomas into prognostic subtypes, with high LanCL1 expression correlating with low tumor grade, favorable molecular features (e.g., IDH1 mutation, 1p/19q co-deletion), and superior patient survival. Functional assays further revealed that LanCL1 inhibited glioma cell growth and migration by coordinately activating mitochondrial metabolism at the transcriptional level and inducing cell cycle arrest via modulation of CDK1/p27 axis. These findings highlight the critical role of redox regulation in glioma pathogenesis and establish LanCL1 as both a prognostic biomarker and potential therapeutic target for exploiting redox vulnerabilities in glioma.

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氧化还原调节剂LanCL1通过协调抑制细胞生长和调节线粒体代谢来抑制胶质瘤的进展。

胶质瘤是一种具有高度侵袭性和异质性的脑肿瘤，临床预后差，迫切需要新的预后生物标志物和治疗靶点。氧化还原调节，平衡活性氧（ROS）的产生和抗氧化防御机制，已成为支持胶质瘤进展的关键适应性机制。然而，氧化还原相关基因在胶质瘤中的确切作用和临床意义仍然不明确。在这里，我们采用综合分析来探索氧化还原相关基因在胶质瘤中的功能影响，并确定LanCL1是胶质瘤恶性肿瘤的关键调节因子。97个氧化还原相关基因的一致聚类将胶质瘤分层为预后亚型，LanCL1的高表达与低肿瘤分级、有利的分子特征（如IDH1突变、1p/19q共缺失）以及较高的患者生存率相关。功能分析进一步表明，LanCL1通过在转录水平上协调激活线粒体代谢，并通过调节CDK1/p27轴诱导细胞周期阻滞，从而抑制胶质瘤细胞的生长和迁移。这些发现强调了氧化还原调控在胶质瘤发病机制中的关键作用，并确立了LanCL1作为预后生物标志物和利用胶质瘤氧化还原脆弱性的潜在治疗靶点。

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

Free Radical Biology and Medicine 医学-内分泌学与代谢

CiteScore

14.00

自引率

4.10%

发文量

850

审稿时长

22 days

期刊介绍： Free Radical Biology and Medicine is a leading journal in the field of redox biology, which is the study of the role of reactive oxygen species (ROS) and other oxidizing agents in biological systems. The journal serves as a premier forum for publishing innovative and groundbreaking research that explores the redox biology of health and disease, covering a wide range of topics and disciplines. Free Radical Biology and Medicine also commissions Special Issues that highlight recent advances in both basic and clinical research, with a particular emphasis on the mechanisms underlying altered metabolism and redox signaling. These Special Issues aim to provide a focused platform for the latest research in the field, fostering collaboration and knowledge exchange among researchers and clinicians.