LncRNA MALAT1 Facilitates Parkinson's Disease Progression by Increasing SOCS3 Promoter Methylation.

IF 3.1 3区医学 Q3 GERIATRICS & GERONTOLOGY

Gerontology Pub Date : 2024-10-16 DOI:10.1159/000541719

Yuqi Liu, Dan Feng, Fenfen Liu, Yun Liu, Fangya Zuo, Yujie Wang, Lanlan Chen, Xiuhong Guo, Jinyong Tian

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引用次数: 0

Abstract

Introduction: Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been shown to be involved in Parkinson's disease (PD) progression, but its mechanism needs to be further explored.

Methods: Mice were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD mice models, and BV2 cells were treated with lipopolysaccharides (LPS) to mimic PD cell models. MALAT1 expression and suppressor of cytokine signaling 3 (SOCS3) protein level were examined using quantitative real-time PCR and Western blot, respectively. Cell functions were tested by cell counting kit 8 assay and flow cytometry. The interaction between MALAT1 and SOCS3 was confirmed using RNA pull-down and RIP assays.

Results: MALAT1 was upregulated in MPTP-induced PD mice and LPS-induced BV2 cells. Silencing of MALAT1 increased viability, while inhibiting apoptosis and inflammation in LPS-induced BV2 cells. Besides, MALAT1 enhanced the SOCS3 promoter methylation to decrease its expression by recruiting DNMT1, DNMT3A, and DNMT3B. Furthermore, SOCS3 knockdown eliminated sh-MALAT1-mediated the inhibition effect on LPS-induced BV2 cell injury. In vivo, MALAT1 silencing ameliorated neurological impairment and neuroinflammation in MPTP-induced PD mice.

Conclusion: Our data revealed that MALAT1 worsened PD processes via inhibiting SOCS3 expression by increasing its promoter methylation.

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LncRNA MALAT1通过增加SOCS3启动子甲基化促进帕金森病的进展。

背景：长非编码RNA转移相关肺腺癌转录本1（MALAT1）已被证实参与帕金森病（PD）的进展，但其机制有待进一步探讨：方法：给小鼠注射1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导帕金森病小鼠模型，用脂多糖（LPS）处理BV2细胞模拟帕金森病细胞模型。分别用实时定量 PCR 和 Western 印迹法检测 MALAT1 表达和细胞因子信号转导抑制因子 3（SOCS3）蛋白水平。细胞计数试剂盒8检测法和流式细胞术检测了细胞功能。通过 RNA pull-down 和 RIP 试验证实了 MALAT1 和 SOCS3 之间的相互作用：结果：MALAT1在MPTP诱导的PD小鼠和LPS诱导的BV2细胞中上调。沉默 MALAT1 可提高 LPS 诱导的 BV2 细胞的活力，同时抑制其凋亡和炎症反应。此外，MALAT1 通过招募 DNMT1、DNMT3A 和 DNMT3B 增强了 SOCS3 启动子甲基化，从而降低了其表达。此外，敲除 SOCS3 可消除 sh-MALAT1 介导的对 LPS 诱导的 BV2 细胞损伤的抑制作用。在体内，MALAT1沉默可改善MPTP诱导的帕金森病小鼠的神经损伤和神经炎症：我们的数据显示，MALAT1通过增加启动子甲基化抑制SOCS3的表达，从而恶化了帕金森病的进程。

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

Gerontology 医学-老年医学

CiteScore

6.00

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： In view of the ever-increasing fraction of elderly people, understanding the mechanisms of aging and age-related diseases has become a matter of urgent necessity. ''Gerontology'', the oldest journal in the field, responds to this need by drawing topical contributions from multiple disciplines to support the fundamental goals of extending active life and enhancing its quality. The range of papers is classified into four sections. In the Clinical Section, the aetiology, pathogenesis, prevention and treatment of agerelated diseases are discussed from a gerontological rather than a geriatric viewpoint. The Experimental Section contains up-to-date contributions from basic gerontological research. Papers dealing with behavioural development and related topics are placed in the Behavioural Science Section. Basic aspects of regeneration in different experimental biological systems as well as in the context of medical applications are dealt with in a special section that also contains information on technological advances for the elderly. Providing a primary source of high-quality papers covering all aspects of aging in humans and animals, ''Gerontology'' serves as an ideal information tool for all readers interested in the topic of aging from a broad perspective.