The diagnostic value and molecular mechanisms of LncRNA ZFAS1 in neuropathic pain

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters Pub Date : 2025-01-18 DOI:10.1016/j.neulet.2024.138097

Yunchao Chu , Jing Chen , Huaqing Cui , Qiuyi Xie , Shasha Mei

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引用次数: 0

Abstract

Objective

Long non-coding RNA (lncRNA) has been playing an increasingly significant role in neuropathic pain (NP). This study aimed to investigate the clinical significance and mechanism of LncRNA ZNFX1 antisense RNA 1 (ZFAS1) in NP.

Methods

92 patients with NP and 85 healthy controls were enrolled, and a rat NP model was constructed by chronic constrictive injury (CCI). LPS-induced microglia BV2 cells were used to construct an in vitro cellular model. RT-qPCR analysis of the mRNA levels of ZFAS1, miR-421, and Iba-1 (markers of microglia activation). Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were used to assess mechanosensitive and thermal nociceptive allergic responses. ELISA assay for pro-inflammatory factors and anti-inflammatory factors expression. ROC assay for the diagnostic value of ZFAS1. Validation of the targeting between ZFAS1 and miR-421 by dual luciferase reporter assay.

Results

ZFAS1 significantly increased while miR-421 significantly decreased in individuals with NP, in a rat model of CCI, and in LPS-induced microglial cells. Functionally, miR-421 directly targeted ZFAS1. ZFAS1 levels could significantly differentiate between NP patients and control (AUC = 0.910). Low expression of ZFAS1 significantly alleviated PWL and PWT in CCI rats. Elevated neuro-proinflammatory factors and decreased anti-inflammatory factors in CCI rats were significantly reversed by low expression of ZFAS1, but this is partially weakened by low expression of miR-421. Moreover, silencing ZFAS1 hindered the upregulation of Iba-1 expression induced by LPS, which was rescued significantly by miR-421.

Conclusion

Elevated ZFAS1 is a potential bio-diagnostic marker for NP. Inhibition of ZFAS1 may alleviate NP progression by inhibiting microglia activation and neuro-inflammatory responses.

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LncRNA ZFAS1在神经性疼痛中的诊断价值及分子机制

目的：长链非编码RNA （lncRNA）在神经性疼痛（NP）中发挥着越来越重要的作用。本研究旨在探讨LncRNA ZNFX1反义RNA 1 （ZFAS1）在NP中的临床意义及作用机制。方法：选取92例NP患者和健康对照，建立慢性缩窄性损伤大鼠NP模型。采用脂多糖诱导的小胶质细胞BV2构建体外细胞模型。RT-qPCR分析ZFAS1、miR-421和Iba-1（小胶质细胞激活标志物）的mRNA水平。用足部戒断阈值（PWT）和足部戒断潜伏期（PWL）评估机械敏感性和热伤害性过敏反应。ELISA法检测促炎因子和抗炎因子的表达。ROC测定ZFAS1的诊断价值。通过双荧光素酶报告基因试验验证ZFAS1和miR-421之间的靶向性。结果：在NP个体、CCI大鼠模型和lps诱导的小胶质细胞中，ZFAS1显著升高，miR-421显著降低。在功能上，miR-421直接靶向ZFAS1。ZFAS1水平在NP患者和对照组之间具有显著差异（AUC = 0.910）。低表达ZFAS1可显著减轻CCI大鼠PWL和PWT。ZFAS1的低表达显著逆转了CCI大鼠神经促炎因子升高和抗炎因子降低，但miR-421的低表达部分削弱了这一点。此外，沉默ZFAS1阻碍了LPS诱导的Iba-1表达上调，miR-421可显著挽救Iba-1表达上调。结论：ZFAS1升高是NP潜在的生物诊断标志物。抑制ZFAS1可能通过抑制小胶质细胞激活和神经炎症反应来缓解NP进展。

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

Neuroscience Letters 医学-神经科学

CiteScore

5.20

自引率

0.00%

发文量

408

审稿时长

50 days

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