LncRNA-CFTBS enhances Mycobacterium tuberculosis survival in macrophages by modulating ferroptosis through the miR-515-5p/miR-519e-5p/SAT1 axis.

IF 5.4 1区农林科学 Q1 IMMUNOLOGY

Virulence Pub Date : 2025-12-01 Epub Date: 2025-10-11 DOI:10.1080/21505594.2025.2545563

Yuxin Li, Yajuan Bai, Chunyu Hei, LiYing Zhao, Wenqi Dong, Chen Tan

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引用次数: 0

Abstract

Tuberculosis (TB) remains one of the primary global causes of death and poses substantial public health challenges. The intracellular survival of Mycobacterium tuberculosis (M.tb) can be influenced by ferroptosis; however, how lipid peroxidation-induced ferroptosis operates during M.tb infection remains unclear. Our study revealed a significantly upregulated lncRNA (lncRNA-cytoplasm-regulating ferroptosis and tuberculosis survival (CFTBS)) that modulates ferroptosis, enhancing M.tb intracellular survival by affecting the lipid peroxidation-related pathway rather than the cystine/GSH/GPX4 pathway. We elucidated that lncRNA-CFTBS competitively binds miR-515-5p and miR-519e-5p, regulating spermidine/spermine N1-acetyltransferase 1 (SAT1) expression, which plays a critical role in increasing the expression of arachidonic acid 15-lipoxygenase (ALOX15) and promoting lipid peroxidation and ferroptosis. Our findings reveal a mechanism by which lncRNA-CFTBS enhances M.tb survival during infection by regulating a noncanonical ferroptosis signalling pathway, offering a deeper understanding of the function of noncoding RNAs in ferroptosis and TB pathogenesis and identifying potential therapeutic targets.

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LncRNA-CFTBS通过miR-515-5p/miR-519e-5p/SAT1轴调节铁凋亡，从而提高结核分枝杆菌在巨噬细胞中的存活。

结核病仍然是全球主要死亡原因之一，并构成重大的公共卫生挑战。铁下垂可影响结核分枝杆菌的细胞内存活；然而，脂质过氧化诱导的铁下垂如何在结核分枝杆菌感染期间发生尚不清楚。我们的研究揭示了lncRNA （lncRNA-胞质调节铁亡和结核存活（CFTBS））的显著上调，该lncRNA通过影响脂质过氧化相关途径而不是胱氨酸/GSH/GPX4途径来调节铁亡，提高M.tb细胞内存活。我们阐明lncRNA-CFTBS竞争性结合miR-515-5p和miR-519e-5p，调节亚精胺/精胺l1 -乙酰转移酶1 （SAT1）的表达，这在增加花生四烯酸15-脂氧合酶（ALOX15）的表达和促进脂质过氧化和铁死亡中起关键作用。我们的研究结果揭示了lncRNA-CFTBS通过调节非典型铁亡信号通路提高M.tb感染期间存活的机制，为深入了解非编码rna在铁亡和TB发病机制中的功能以及确定潜在的治疗靶点提供了新的思路。

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

Virulence IMMUNOLOGY-MICROBIOLOGY

CiteScore

9.20

自引率

1.90%

发文量

123

审稿时长

6-12 weeks

期刊介绍： Virulence is a fully open access peer-reviewed journal. All articles will (if accepted) be available for anyone to read anywhere, at any time immediately on publication. Virulence is the first international peer-reviewed journal of its kind to focus exclusively on microbial pathogenicity, the infection process and host-pathogen interactions. To address the new infectious challenges, emerging infectious agents and antimicrobial resistance, there is a clear need for interdisciplinary research.