The PRMT2/FOXA2/miR-323-3p/Kv2.1 signaling axis in sensory neurons controls neuropathic pain
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ABSTRACT:
PROVIDER: PRJNA932751 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23372009_1.fastq.gz | Fastqsanger.gz | |||
| SRR23372009_2.fastq.gz | Fastqsanger.gz | |||
| SRR23372010_1.fastq.gz | Fastqsanger.gz | |||
| SRR23372010_2.fastq.gz | Fastqsanger.gz | |||
| SRR23372011_1.fastq.gz | Fastqsanger.gz |
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Project description:Although miRNA-mediated epigenetic regulation has been investigated as a potential therapeutic strategy for diseases, its exact functional regulatory contributions to neuropathic pain have not yet been fully elucidated. Herein, we revealed miR-323-3p as a key functional noncoding RNA in modulating trigeminal neuropathic pain. Through combined high-throughput sequencing and qPCR analysis, we revealed that miR-323-3p was most significantly upregulated in the injured trigeminal ganglion (TG). The administration of a miR-323-3p antagomir via intra-TG injection or blockade of miR-323-3p through lentiviral delivery specifically targeting neurons in injured TGs suppressed established trigeminal neuropathic pain. While miR-323-3p inhibition had no effect on inflammatory pain, local induction of miR-323-3p in naive TGs directly elicited pain hypersensitivity. Mechanistically, nerve injury caused upregulated protein expression of arginine methyltransferase 2 (PRMT2), which promotes asymmetric demethylation of H3R8 (H3R8me2a), thereby facilitating the binding of the forkhead box A2 (FOXA2) transcription factor to the miR-323-3p promoter and resulting in the upregulation of miR-323-3p expression. Furthermore, the increase in miR-323-3p expression induced significant reductions in Kv2.1 protein expression and channel currents, resulting in TG neuronal hyperexcitability. Conversely, downregulation of miR-323-3p in the injured TG reversed the decrease in Kv2.1 expression and attenuated nerve injury-induced mechanical allodynia. Thus, miR-323-3p upregulation is causally involved in the development of trigeminal neuropathic pain through the regulation of Kv2.1 channels in the TG. The mechanistic understanding of the PRMT2/FOXA2/miR-323-3p/Kv2.1 signaling axis in sensory neurons may enable the discovery of new therapeutic targets for neuropathic pain management.
2025-06-08 | GSE224814 | GEO
Project description:Nerve injury-induced changes in gene expression in primary sensory neurons, such as trigeminal ganglion (TG) neurons, play a critical role in the genesis of neuropathic pain. Therefore, understanding the molecular mechanisms underlying these changes in the TGs following peripheral nerve injury will enable us to develop a new avenue for managing trigeminal-mediated neuropathic pain. Studies have highlighted the involvement of miRNA-mediated modulation in a wide range of diseases, leading to the exploration of miRNA-based therapeutics as a potential treatment strategy. Here, in this RNA-seq database, we have found that microRNA-216a-3p (miR-216a-3p) and miR-32-5p (miR-32-5p), which are downregulated in injured TGs, are novel functional RNAs involved in regulating trigeminal-mediated neuropathic pain. Histone methylation-mediated miRNA downregulation in TG neurons regulates trigeminal neuropathic pain by targeting either STIM1 (H3K27me3/SOX10/miR-216a-3p/STIM1) or Cav3.2 (GR/miR-32-5p/Cav3.2) channels. Moreover, we found that miR-323-3p exhibited the most significant upregulation in the injured TG. Understanding the mechanistic role of the PRMT2/FOXA2/miR-323-3p/Kv2.1 signaling axis in sensory neurons may advance the discovery of novel therapeutic strategies for neuropathic pain.
2025-01-08 | GSE192803 | GEO
Project description:Hypoxia-inducible transcription factors (HIFs) are crucial transcription factors for cellular response to low oxygen levels, but the key mediators for their downstream transcription activation are not well characterized. We previously found that PRMT2 activates target gene expression through its methyltransferase activity on histone H3R8. Here we find that PRMT2 expression is activated by HIF1 at hypoxic conditions. And PRMT2 activity is widely required for hypoxia-induced transcription activation. Accordingly, PRMT2 inactivation alleviates hypoxia-induced glioblastoma progression and chemotherapeutic resistance. And PRMT2 expression is associated with hypoxia signature
2024-04-01 | GSE235438 | GEO
Project description:This program addresses the gene signature associated with DRG in the Chung rat model for neuropathic pain. The Chung neuropathic pain profiling data was analyzed by identifying genes that were up- and down-regulated at selected p value and fold change in DRG of the Sprague Dawley rats following spinal nerve ligation compared to the sham-operated controls.
2013-03-22 | E-GEOD-38038 | biostudies-arrayexpress
Project description:• Project description: Why only half of the idiopathic peripheral polyneuropathy (IPN) patients develop neuropathic pain is unknown. By conducting a proteomics analysis on IPN patients, we aimed to discover proteins and new pathways that are associated with neuropathic pain. We conducted unbiased mass-spectrometry proteomics analysis on blood plasma from 31 IPN patients with severe neuropathic pain and 29 IPN patients with no pain, to investigate protein biomarkers and protein-protein interactions associated with neuropathic pain. Univariate modeling was done with Linear mixed modeling (LMM) and corrected for multiple testing. Multivariate modelling was performed using elastic net analysis and validated with internal cross validation and bootstrapping.
2025-02-19 | PXD046464 | Pride
Project description:Peripheral nerve injury alters the expression of hundreds of proteins in dorsal root ganglia (DRG). Targeting some of these proteins has led to successful treatments for acute pain, but not for sustained postoperative neuropathic pain. The latter may require targeting multiple proteins. Since a single microRNA (miR) can affect the expression of multiple proteins, here, we describe an approach to identify chronic neuropathic pain-relevant miRs. We used two variants of the spared nerve injury (SNI): Sural-SNI and Tibial-SNI and found distinct pain phenotypes between the two. Both models induced strong mechanical allodynia, but only Sural-SNI rats maintained strong mechanical and cold allodynia, as previously reported. In contrast, we found that Tibial-SNI rats recovered from mechanical allodynia and never developed cold allodynia. Since both models involve nerve injury, we increased the probability of identifying differentially regulated miRs that correlated with the quality and magnitude of neuropathic pain and decreased the probability of detecting miRs that are solely involved in neuronal regeneration. We found seven such miRs in L3-L5 DRG. The expression of these miRs increased in Tibial-SNI. These miRs displayed a lower level of expression in Sural-SNI, with four having levels lower than those in sham animals. Bioinformatics analysis of how these miRs could affect the expression of some ion channels supports the view that, following a peripheral nerve injury, the increase of the 7 miRs may contribute to the recovery from neuropathic pain while the decrease of four of them may contribute to the development of chronic neuropathic pain. The approach used resulted in the identification of a small number of potentially neuropathic pain relevant miRs. Additional studies are required to investigate whether manipulating the expression of the identified miRs in primary sensory neurons can prevent or ameliorate chronic neuropathic pain following peripheral nerve injuries. To identify the miRs that were differentially dysregulated between Tibial-SNI and Sural-SNI, we first performed 12 microarrays in a limited number of samples (in four individual DRGs per group: Sham, Tibial-SNI and Sural-SNI; two L3-DRG and two L4-DRG). Then, miRs identified as having differential expression were corroborated with real time qRT-PCR in RNA isolated from individual DRGs (L3, L4 and L5) derived from 4 rats per group (not presented here, but in the manuscript).
2014-09-29 | E-GEOD-60033 | biostudies-arrayexpress
Project description:Here we show that PRMT2 is highly expressed in GBM, which is correlated with poor prognosis. The silencing of PRMT2 inhibits GBM cell growth and glioblastoma stem cell self-renewal in vitro and suppreses orthotopic tumor growth. Transcriptome analysis demonstrated that PRMT2 depletion leads to significant deregulation of genes mainly associated with cell cycle progression and pathways in cancer. In agreement with previously published results, we show that PRMT2 is responsible for H3R8 asymmetric methylation (H3R8me2a) and that H3R8me2a enrichment at promoters and enhancers is closely correlated with known active histone marks. Furthermore, we show that PRMT2-mediated H3R8me2a is required for the maintenance of target gene expression and that the catalytic activity of PRMT2 is required for its protumorigenic functions. Taken together, this study demonstrates that PRMT2 acts as a transcriptional co-activator for oncogenic gene expression programs in GBM pathogenesis and provides a rationale for PRMT2 targeting in aggressive gliomas.
2018-08-22 | GSE110424 | GEO
Project description:To further characterize the downstream targets of uc.323, we performed global microarray analysis after knockdown of uc.323 in cardiomyocytes to gain broad insight into uc.323-mediated transcriptome changes.
2019-11-30 | GSE141166 | GEO
Project description:This program addresses the gene signature associated with DRG in the Chung rat model for neuropathic pain.
2013-03-22 | GSE38038 | GEO
Project description:Arginine methylation is catalyzed by protein arginine methyltransferases (PRMTs) and is involved in various cellular processes, including cancer development. PRMT2 expression is increased in several cancer types although its role in acute myeloid leukemia (AML) remains unknown. Here, we investigate the role of PRMT2 in a cohort of patients with AML, PRMT2 knockout AML cell lines as well as a Prmt2 knockout mouse model. In patients, low PRMT2 expressors are enriched for inflammatory signatures, including the NF-κB pathway, and show inferior survival. In keeping with a role for PRMT2 in control of inflammatory signaling, bone marrow-derived macrophages from Prmt2 KO mice display increased pro-inflammatory cytokine signaling upon LPS treatment. In PRMT2-depleted AML cell lines, aberrant inflammatory signaling has been linked to overproduction of IL6, resulting from a deregulation of the NF-κB signaling pathway, therefore leading to hyperactivation of STAT3. Together, these findings identify PRMT2 as a key regulator of inflammation in AML.
2024-05-17 | GSE266252 | GEO