MiR‐223‐3p alleviates trigeminal neuropathic pain in the male mouse by targeting MKNK2 and MAPK/ERK signaling

Huang, Bixia; Guo, Shaoyong; Zhang, Yi-Pan; Lin, Peng-Xing; Lin, Changgui; Chen, Meixia; Zhu, Sheng-Yin; Huang, Liyu; He, Junwei; Zhang, Lingfeng; Zheng, Yanping; Wen, Zhipeng

doi:10.1002/brb3.2634

Cited by 10 publications

(4 citation statements)

References 48 publications

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“…Significant downregulation of miR-223-3p has been previously reported in fibromyalgia patients ( Bjersing et al, 2013 ). Furthermore, upregulation of miR-223-3p could alleviate trigeminal neuralgia NP through targeting MKNK2 and MAPK/ERK signals ( Huang et al, 2022 ). In addition, over-expression of miR-223-3p induced by electroacupuncture significantly reduces postherpetic neuralgia pain by inhibiting neuron cell autophagy ( Toyama et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenetic landscape of pain management variants among Mediterranean populations

Jmel,

Boukhalfa,

Gouiza

et al. 2024

Front. Pharmacol.

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Background:Chronic pain is a major socioeconomic burden in the Mediterranean region. However, we noticed an under-representation of these populations in the pharmacogenetics of pain management studies. In this context, we aimed 1) to decipher the pharmacogenetic variant landscape among Mediterranean populations compared to worldwide populations in order to identify therapeutic biomarkers for personalized pain management and 2) to better understand the biological process of pain management through in silico investigation of pharmacogenes pathways.Materials and Methods:We collected genes and variants implicated in pain response using the Prisma guidelines from literature and PharmGK database. Next, we extracted these genes from genotyping data of 829 individuals. Then, we determined the variant distribution among the studied populations using multivariate (MDS) and admixture analysis with R and STRUCTURE software. We conducted a Chi2 test to compare the interethnic frequencies of the identified variants. We used SNPinfo web server, miRdSNP database to identify miRNA-binding sites. In addition, we investigated the functions of the identified genes and variants using pathway enrichment analysis and annotation tools. Finally, we performed docking analysis to assess the impact of variations on drug interactions.Results:We identified 63 variants implicated in pain management. MDS analysis revealed that Mediterranean populations are genetically similar to Mexican populations and divergent from other populations. STRUCTURE analysis showed that Mediterranean populations are mainly composed of European ancestry. We highlighted differences in the minor allele frequencies of three variants (rs633, rs4680, and rs165728) located in the COMT gene. Moreover, variant annotation revealed ten variants with potential miRNA-binding sites. Finally, protein structure and docking analysis revealed that two missense variants (rs4680 and rs6267) induced a decrease in COMT protein activity and affinity for dopamine.Conclusion:Our findings revealed that Mediterranean populations diverge from other ethnic groups. Furthermore, we emphasize the importance of pain-related pathways and miRNAs to better implement these markers as predictors of analgesic responses in the Mediterranean region.

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Section: Discussionmentioning

confidence: 99%

Pharmacogenetic landscape of pain management variants among Mediterranean populations

Jmel,

Boukhalfa,

Gouiza

et al. 2024

Front. Pharmacol.

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“…Encouragingly, limited research has preliminarily revealed the involvement of miR-223-3p in NeP. For example, trigeminal NeP can be alleviated by miR-223-3p targeting MKNK2 and MAPK/ERK signals in male mice ( Huang et al, 2022 ). Another study also reported that electroacupuncture inhibits autophagy in neuronal cells by increasing the expression of miR-223-3p in postherpetic neuralgia ( Zou et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Systematic identification of potential key microRNAs and circRNAs in the dorsal root ganglia of mice with sciatic nerve injury

Youfen

Xu²,

Lin³

et al. 2023

Front. Mol. Neurosci.

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BackgroundNeuropathic pain (NeP) is a pathological condition arising from a lesion or disease affecting the somatosensory system. Accumulating evidence has shown that circular RNAs (circRNAs) exert critical functions in neurodegenerative diseases by sponging microRNAs (miRNAs). However, the functions and regulatory mechanisms of circRNAs as competitive endogenous RNAs (ceRNAs) in NeP remain to be determined.MethodsThe sequencing dataset GSE96051 was obtained from the public Gene Expression Omnibus (GEO) database. First, we conducted a comparison of gene expression profiles in the L3/L4 dorsal root ganglion (DRG) of sciatic nerve transection (SNT) mice (n = 5) and uninjured mice (Control) (n = 4) to define the differentially expressed genes (DEGs). Then, critical hub genes were screened by exploring protein–protein interaction (PPI) networks with Cytoscape software, and the miRNAs bound to them were predicted and selected and then validated by qRT-PCR. Furthermore, key circRNAs were predicted and filtered, and the network of circRNA-miRNA-mRNA in NeP was constructed.ResultsA total of 421 DEGs were identified, including 332 upregulated genes and 89 downregulated genes. Ten hub genes, including IL6, Jun, Cd44, Timp1, and Csf1, were identified. Two miRNAs, mmu-miR-181a-5p and mmu-miR-223-3p, were preliminarily verified as key regulators of NeP development. In addition, circARHGAP5 and circLPHN3 were identified as key circRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that these differentially expressed mRNAs and targeting miRNAs were involved in signal transduction, positive regulation of receptor-mediated endocytosis and regulation of neuronal synaptic plasticity. These findings have useful implications for the exploration of new mechanisms and therapeutic targets for NeP.ConclusionThese newly identified miRNAs and circRNAs in networks reveal potential diagnostic or therapeutic targets for NeP.

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“…miR-223 overexpression with a lentiviral vector improves the behavioural response to mechanical stimuli and restores MAPKs phosphorylation levels. The effect of miR-223 may occur through the direct interaction with the translational repressor MKNK2, involved in the MAPK pathways [ 42 ].…”

Section: Microrna Involvement In Pain Pathwaysmentioning

confidence: 99%

The Role of miRNAs in Neuropathic Pain

et al. 2023

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Neuropathic pain is a debilitating condition affecting around 8% of the adult population in the UK. The pathophysiology is complex and involves a wide range of processes, including alteration of neuronal excitability and synaptic transmission, dysregulated intracellular signalling and activation of pro-inflammatory immune and glial cells. In the past 15 years, multiple miRNAs–small non-coding RNA–have emerged as regulators of neuropathic pain development. They act by binding to target mRNAs and preventing the translation into proteins. Due to their short sequence (around 22 nucleotides in length), they can have hundreds of targets and regulate several pathways. Several studies on animal models have highlighted numerous miRNAs that play a role in neuropathic pain development at various stages of the nociceptive pathways, including neuronal excitability, synaptic transmission, intracellular signalling and communication with non-neuronal cells. Studies on animal models do not always translate in the clinic; fewer studies on miRNAs have been performed involving human subjects with neuropathic pain, with differing results depending on the specific aetiology underlying neuropathic pain. Further studies using human tissue and liquid samples (serum, plasma, saliva) will help highlight miRNAs that are relevant to neuropathic pain diagnosis or treatment, as biomarkers or potential drug targets.

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MiR‐223‐3p alleviates trigeminal neuropathic pain in the male mouse by targeting MKNK2 and MAPK/ERK signaling

Cited by 10 publications

References 48 publications

Pharmacogenetic landscape of pain management variants among Mediterranean populations

Pharmacogenetic landscape of pain management variants among Mediterranean populations

Systematic identification of potential key microRNAs and circRNAs in the dorsal root ganglia of mice with sciatic nerve injury

The Role of miRNAs in Neuropathic Pain

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