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LncRNA PCAT19 Regulates Neuropathic Pain via Regulation of miR-182-5p/JMJD1A in a Rat Model of Chronic Constriction Injury
Neuroimmunomodulation ( IF 2.2 ) Pub Date : 2021-09-09 , DOI: 10.1159/000518847
Miao Huo 1 , Xingxing Zheng 1 , Ning Bai 1 , Ruifen Xu 1 , Guang Yang 1 , Ziyu Zhao 1
Affiliation  

Introduction: Neuropathic pain (NP) is one of the most severe chronic pain types. In recent years, more and more studies have shown that long noncoding RNA (LncRNA) plays a key role in a variety of human diseases, including NP. However, the role of LncRNA prostate cancer-associated transcript 19 (PCAT19) in NP and its specific mechanism remain unclear. Methods: A chronic constrictive injury (CCI) rat model was established. Rat paw withdrawal threshold and paw withdrawal latency were used to evaluate the neuronal pain behavior of rats in this model. mRNA expression of PCAT19, neuroinflammatory factor, microRNA (miR)-182-5p, and Jumonji domain containing 1A (JMJD1A) were detected by quantitative real-time PCR. ELISA analysis was used to detect inflammatory factor protein expression. Dual-luciferase reporter assay was used to evaluate the targeting relationship between genes. Results: PCAT19 was continuously upregulated in CCI rats. miR-182-5p was the target of PCAT19, and miR-182-5p was increased after PCAT19 knockdown. NP behaviors such as mechanical ectopic pain and thermal hyperalgesia as well as neuroinflammation can be reduced by knocking down PCAT19. However, the injection of miR-182-5p antagomir significantly reversed the level of the NP behaviors and neuroinflammation caused by PCAT19 knockdown. Besides, dual-luciferase reporter assay showed that JMJD1A was the target gene of miR-182-5p. The level of JMJD1A in CCI rats increased with time. After PCAT19 knockdown, JMJD1A was significantly decreased, but inhibition of miR-182-5p can reverse its levels. Conclusion: This study shows that PCAT19 plays a role in NP by targeting the miR-182-5p/JMJD1A axis, and PCAT19 can be used as a new therapeutic target for NP.
Neuroimmunomodulation


中文翻译:

LncRNA PCAT19 通过调节慢性收缩损伤大鼠模型中的 miR-182-5p/JMJD1A 来调节神经性疼痛

简介:神经性疼痛(NP)是最严重的慢性疼痛类型之一。近年来,越来越多的研究表明,长链非编码RNA(LncRNA)在包括NP在内的多种人类疾病中发挥着关键作用。然而,LncRNA前列腺癌相关转录物19(PCAT19)在NP中的作用及其具体机制仍不清楚。方法:建立慢性缩窄性损伤(CCI)大鼠模型。大鼠缩爪阈值和缩爪潜伏期用于评价该模型大鼠的神经元疼痛行为。通过定量实时PCR检测PCAT19、神经炎症因子、microRNA(miR)-182-5p和含有1A(JMJD1A)的Jumonji结构域的mRNA表达。ELISA分析用于检测炎症因子蛋白表达。双荧光素酶报告基因检测用于评估基因之间的靶向关系。结果:PCAT19 在 CCI 大鼠中持续上调。miR-182-5p 是 PCAT19 的靶点,PCAT19 敲低后 miR-182-5p 增加。通过敲除 PCAT19 可以减少 NP 行为,例如机械异位疼痛和热痛觉过敏以及神经炎症。然而,注射 miR-182-5p antagomir 显着逆转了由 PCAT19 敲低引起的 NP 行为和神经炎症水平。此外,双荧光素酶报告基因检测显示JMJD1A是miR-182-5p的靶基因。CCI大鼠中JMJD1A的水平随时间增加。PCAT19 敲低后,JMJD1A 显着降低,但抑制 miR-182-5p 可以逆转其水平。结论:本研究表明PCAT19通过靶向miR-182-5p/JMJD1A轴在NP中发挥作用,PCAT19可作为NP的新治疗靶点。
神经免疫调节
更新日期:2021-09-09
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