MicroRNA-146a-5p attenuates neuropathic pain via suppressing TRAF6 signaling in the spinal cord

Lu, Ying; Cao, De‐Li; Jiang, Bao‐Chun; Yang, Tian; Gao, Yong‐Jing

doi:10.1016/j.bbi.2015.04.018

Cited by 100 publications

(85 citation statements)

References 49 publications

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“…However, although several studies have reported that IRAK1 and TRAF6 were downregulated following miRNA-146a overexpression [14–18], the overexpression did not appear to be responsible for the responses that were observed following SCI recovery.…”

Section: Discussionmentioning

confidence: 93%

“…miRNA-146a has been certified to downregulate its target genes TNF receptor-associated factor 6 ( TRAF6 ) and IL-1 receptor-associated kinase 1 ( IRAK1 ), which leads to the inhibition of the inflammatory reaction in macrophages, monocytes, astrocytes, and neurons [14–17]. Also, Lu et al [18] demonstrated that miRNA-146a could attenuate neuropathic pain by suppressing TRAF6 signaling in the spinal cord.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-146a Contributes to SCI Recovery via Regulating TRAF6 and IRAK1 Expression

Wei

Wang

Zhou

et al. 2016

BioMed Research International

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MicroRNA-146a participates in spinal cord injury (SCI) recovery. Until recently, how miRNA-146a participates in SCI remained unclear. In this study, we tried to explore the roles of miRNA-146a in the recovery of SCI using a rat model. The expression of the probable target genes of miRNA-146a (including IRAK1 and TARF6) as well as proinflammation cytokines were measured until 7 days after surgery in the three groups (sham group, SCI group, and miRNA-146a antagomir injection group). Also, the animals' motivations were estimated using Basso Beattie Bresnahan (BBB) during the whole experiment. A luciferase assay was performed to demonstrate that miRNA-146a could directly target the mRNAs of IRAK1 and TRAF6. Our experiments indicate that miRNA-146a inhibits proinflammatory cytokine secretion by suppressing IRAK1 and TRAF6 expression in the SCI model. In contrast, miRNA-146a may be upregulated by inflammatory mediators via the IRAK1/TRAF6 pathway in the spinal cord. As a negative feedback element, miRNA-146a could make sure that the expression of IRAK1- and TRAF6-mediated genes was under tight control. Thus, miRNA-146a may serve as a novel therapeutic target for SCI interventions.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

MicroRNA-146a Contributes to SCI Recovery via Regulating TRAF6 and IRAK1 Expression

Wei

Wang

Zhou

et al. 2016

BioMed Research International

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“…Binding of the let-7 family of miRNAs to the 3′-UTR of OPRM1 suggests their involvement in opioid tolerance [22], and therefore the observed upregulation of let-7a-5p may reflect negative feedback response against MOR stimulation. miR-146a-5p was observed to be upregulated upon morphine treatment in human monocyte-derived macrophages [23] and was reported to play a role in pain signaling [24]. A previous study demonstrated that miR-23b-3p is upregulated by morphine and is involved in the modulation of MOR signaling [25].…”

Section: Discussionmentioning

confidence: 99%

Identification of Circulating miRNAs Differentially Regulated by Opioid Treatment

Toyama

Kiyosawa

Watanabe

et al. 2017

IJMS

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Emerging evidence demonstrates functional contributions of microRNAs (miRNAs) to μ-opioid receptor (MOR) signaling, but the information so far has been mostly limited to their intracellular regulatory mechanisms. The present study aimed to investigate changes in plasma miRNA profiles elicited by opioid treatment in blood samples collected from clinical studies. Healthy male subjects were orally administered with hydromorphone or oxycodone and blood samples were collected at a specified time after the drug treatment. A total of 179 plasma miRNAs were measured using multiplex qRT-PCR. Nine and seventeen miRNAs were commonly upregulated (let-7a-5p, miR-423-3p, miR-199a-3p, miR-146a-5p, miR-23b-3p, miR-24-3p, miR-221-3p, miR-223-3p, and miR-146b-5p) and downregulated (miR-144-3p, miR-215, miR-363-3p, etc.), respectively, following opioid treatment. The MOR signaling-associated miRNAs, namely let-7 family miRNAs (i.e., let-7d-5p, let-7f-5p, let-7c, let-7e-5p), miR-103a-3p, miR-339-3p, miR-146a-5p, miR-23b-3p, miR-23a-3p, and miR-181a-5p, were differentially expressed following drug treatment. These differentially expressed miRNAs are circulating biomarker candidates that can be used to evaluate MOR stimulation and serve as novel clinical diagnostic tools for improving clinical outcomes.

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“…( D ) ncRNAs and their targets in the spinal cord and DRG (listed in the respective dashed boxes) involved in neuropathic pain following SNI or ScNI in mice or rats. ncRNAs include analgesic miRNAs (miR-7a, miR-183, miR-146a-5p) 80– 82 and pain-promoting long non-coding RNA (Kcna2 antisense RNA) 79 or miRNAs (miR-195, miR-221, miR-132-3p) 83– 85 . ↓, downregulation; ↑, upregulation; ?, unidentified target; ATG14 , gene encoding protein that facilitates autophagy; BDNF, brain-derived neurotrophic factor; CpG, cytosine–phosphate–guanine dinucleotide; DRG, dorsal root ganglion; Kv, voltage-gated potassium channel; miRNA, microRNA; MOR, µ-opioid receptor; Nav, voltage-gated sodium channel; ncRNA, non-coding RNA; ScNI, sciatic nerve injury; SNI, spinal nerve injury; SOCS1, suppressor of cytokine signaling 1, a protein suppressing cytokine signaling; TRAF6, tumor necrosis factor (TNF) receptor associated factor 6, an adapter protein mediating TNF-α signaling.…”

Section: Microgliamentioning

confidence: 99%

“…SNI-induced miR-183 downregulation was restored by spinal viral miR-183 delivery, resulting in decreased expression of Nav1.3 and BDNF mRNAs in DRG and diminished hypersensitivity in rats 81 . Also, spinally applied miR-146a-5p mimic (a synthetic double-stranded RNA that mimics endogenous miR-146a-5p) reduced SNI-induced hypersensitivity in mice, probably by suppressing TNF receptor-associated factor 6, an adapter protein mediating signaling of TNF-α 82 . Together, these studies indicate the restoration of analgesic miR-7a, miR-183, and miR-146a-5p as potential neuropathic pain treatments.…”

Section: Non-coding Rnasmentioning

confidence: 99%

Recent advances in understanding neuropathic pain: glia, sex differences, and epigenetics

Machelska

Celik

2016

F1000Res

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Neuropathic pain results from diseases or trauma affecting the nervous system. This pain can be devastating and is poorly controlled. The pathophysiology is complex, and it is essential to understand the underlying mechanisms in order to identify the relevant targets for therapeutic intervention. In this article, we focus on the recent research investigating neuro-immune communication and epigenetic processes, which gain particular attention in the context of neuropathic pain. Specifically, we analyze the role of glial cells, including microglia, astrocytes, and oligodendrocytes, in the modulation of the central nervous system inflammation triggered by neuropathy. Considering epigenetics, we address DNA methylation, histone modifications, and the non-coding RNAs in the regulation of ion channels, G-protein-coupled receptors, and transmitters following neuronal damage. The goal was not only to highlight the emerging concepts but also to discuss controversies, methodological complications, and intriguing opinions.

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MicroRNA-146a-5p attenuates neuropathic pain via suppressing TRAF6 signaling in the spinal cord

Cited by 100 publications

References 49 publications

MicroRNA-146a Contributes to SCI Recovery via Regulating TRAF6 and IRAK1 Expression

MicroRNA-146a Contributes to SCI Recovery via Regulating TRAF6 and IRAK1 Expression

Identification of Circulating miRNAs Differentially Regulated by Opioid Treatment

Recent advances in understanding neuropathic pain: glia, sex differences, and epigenetics

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