LncRNA-84277 is involved in chronic pain-related depressive behaviors through miR-128-3p/SIRT1 axis in central amygdala.

LncRNA-84277 is involved in chronic pain-related depressive behaviors through miR-128-3p/SIRT1 axis in central amygdala.
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DOI:
10.3389/fnmol.2022.920216
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发表时间:
2022
影响因子:
4.8
通讯作者:
Zhou C
Zhou C
中科院分区:
医学2区
文献类型:
--
作者:
Jiao X;Wang R;Ding X;Yan B;Lin Y;Liu Q;Wu Y;Zhou C

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长期的慢性疼痛会导致抑郁症。然而,慢性疼痛相关抑郁症的机制仍不清楚。Sirtuin 1(SIRT 1)是一种依赖于NAD+的组蛋白脱乙酰酶(HDAC)。我们先前的研究已经证明杏仁核中央核(CeA)中的SIRT 1参与慢性疼痛相关抑郁症的发展。此外,越来越多的研究表明,长链非编码RNA(lncRNA)在疼痛或抑郁症的发病机制中起着至关重要的作用。然而,lncRNA是否参与SIRT 1介导的慢性疼痛相关抑郁症仍在很大程度上未知。在这项研究中,我们确定了一个新的lncRNA-84277在CeA的上游分子调节SIRT 1的表达。在功能上,lncRNA-84277在CeA中的过表达显著减轻了保留神经损伤(SNI)诱导的慢性疼痛大鼠的抑郁样行为,而lncRNA-84277在CeA中的敲低诱导了幼稚大鼠的抑郁样行为。从机制上讲,lncRNA-84277作为竞争性内源性RNA(ceRNA)通过竞争性海绵化miR-128- 3 p上调SIRT 1表达,从而改善慢性疼痛相关抑郁样行为。我们的研究结果揭示了lncRNA-84277在CeA中的关键作用,特别是通过ceRNA机制预防慢性疼痛相关抑郁症,并为慢性疼痛相关抑郁症提供了潜在的治疗靶点。
Long-term chronic pain can lead to depression. However, the mechanism underlying chronic pain-related depression remains unclear. Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase (HDAC). Our previous studies have demonstrated that SIRT1 in the central nucleus of the amygdala (CeA) is involved in the development of chronic pain-related depression. In addition, increasing studies have indicated that long non-coding RNAs (lncRNAs) play a vital role in the pathogenesis of pain or depression. However, whether lncRNAs are involved in SIRT1-mediated chronic pain-related depression remains largely unknown. In this study, we identified that a novel lncRNA-84277 in CeA was the upstream molecule to regulate SIRT1 expression. Functionally, lncRNA-84277 overexpression in CeA significantly alleviated the depression-like behaviors in spared nerve injury (SNI)-induced chronic pain rats, whereas lncRNA-84277 knockdown in CeA induced the depression-like behaviors in naïve rats. Mechanically, lncRNA-84277 acted as a competing endogenous RNA (ceRNA) to upregulate SIRT1 expression by competitively sponging miR-128-3p, and therefore improved chronic pain-related depression-like behaviors. Our findings reveal the critical role of lncRNA-84277 in CeA specifically in guarding against chronic pain-related depression via a ceRNA mechanism and provide a potential therapeutic target for chronic pain-related depression.
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