H3K27 trimethylation-mediated downregulation of miR-216a-3p in sensory neurons regulates neuropathic pain behaviors via targeting STIM1 DOI
Yufang Sun, Tao Yu, Junping Cao

et al.

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 45(1), P. e0607242024 - e0607242024

Published: Nov. 26, 2024

Although the therapeutic potential of microRNA-mediated gene regulation has been investigated, its precise functional regulatory mechanism in neuropathic pain remains incompletely understood. In this study, we elucidate that miR-216a-3p serves as a critical noncoding RNA involved modulation trigeminal-mediated pain. By conducting RNA-seq and qPCR analysis, observed notable decrease injured trigeminal ganglia (TG) male rats. Intra-TG administration agomir or lentiviral-mediated overexpression specifically sensory neurons TGs alleviated established behaviors, while downregulation (pharmacologically genetically) naive rats induced behaviors. Moreover, nerve injury significantly elevated histone H3 lysine-27 (H3K27) trimethylation (H3K27me3) levels ipsilateral TG, thereby suppressing SRY-box TF 10 (SOX10) binding to promoter resulting reduction miR-216a-3p. Inhibiting enzymes responsible for catalyzing H3K27me3 restored injury-induced expression markedly ameliorated Furthermore, targeted stromal interaction molecule 1 (STIM1), decreased associated with caused significant upregulation protein abundance STIM1. Conversely, TG suppressed STIM1 reversed mechanical allodynia. Together, mechanistic understanding H3K27me3-dependent SOX10/miR-216a-3p/STIM1 signaling axial may facilitate discovery innovative strategies management.

Language: Английский

Insights into the m6A demethylases FTO and ALKBH5 : structural, biological function, and inhibitor development DOI Creative Commons

Zewei Gao,

Xuan Zha,

Min Li

et al.

Cell & Bioscience, Journal Year: 2024, Volume and Issue: 14(1)

Published: Aug. 27, 2024

Abstract N6-methyladenosine (m 6 A) is dynamically regulated by methyltransferases (termed “writers”) and demethylases (referred to as “erasers”), facilitating a reversible modulation. Changes in m A levels significantly influence cellular functions, such RNA export from the nucleus, mRNA metabolism, protein synthesis, splicing. They are intricately associated with spectrum of pathologies. Moreover, dysregulation modulation has emerged promising therapeutic target across many diseases. plays pivotal role controlling vital downstream molecules critical biological pathways, contributing pathogenesis evolution numerous conditions. This review provides an overview demethylases, explicitly detailing structural functional characteristics FTO ALKBH5. Additionally, we explore their distinct involvement various diseases, examine factors regulating expression, discuss progress inhibitor development.

Language: Английский

Citations

6
M6A Demethylase ALKBH5 in Human Diseases: From Structure to Mechanisms DOI Creative Commons

Miaochun Fang,

Liwen Ye,

Yue Zhu

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 157 - 157

Published: Jan. 21, 2025

N6-methyladenosine (m6A) is the most abundant, dynamically reversible, and evolutionarily conserved internal chemical modification in eukaryotic RNA. It emerging as critical for regulating gene expression at post-transcriptional level by affecting RNA metabolism through, example, pre-mRNA processing, mRNA decay, translation. ALKBH5 has recently been identified an endogenous m6A demethylase implicated a multitude of biological processes. This review provides overview structural functional characteristics involvement diverse human diseases, including metabolic, immune, reproductive, nervous system disorders, well development inhibitors. In summation, this highlights current understanding structure, functions, detailed mechanisms various physiological pathological processes valuable insights clinical applications foundational research within related fields.

Language: Английский

Citations

0
Inhibition of FOXD3 O-GlcNAc Modification Ameliorates Spinal Cord Injury by Promoting STUB1-Mediated Ubiquitination Degradation of HMGB1 DOI
Wu Zhou, Bo Hei, Yihao Liu

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Language: Английский

Citations

0
Mechanism of N6-Methyladenosine Modification in the Pathogenesis of Depression DOI

Zhuohang Xian,

Liangchen Tian, Zai‐Fu Yao

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 18, 2024

Language: Английский

Citations

2
Advances in the pathological mechanisms and clinical treatments of chronic visceral pain DOI Creative Commons
Yongchang Li,

Fu‐Chao Zhang,

Timothy W. Xu

et al.

Molecular Pain, Journal Year: 2024, Volume and Issue: 20

Published: Jan. 1, 2024

Chronic visceral pain stems from internal organs and is frequently associated with functional gastrointestinal disorders, like irritable bowel syndrome (IBS). Since the underlying mechanisms of remain largely unclear, clinical management often limited ineffective. Comprehensive research into pathogenesis pain, along development personalized therapeutic strategies, crucial for advancing treatment options. Studies suggest that imbalances in purinergic receptors neural circuit function are closely linked to onset pain. In this review, we will explore etiology pathological a focus on ion channels, epigenetic factors, circuits, using disorders as case studies. Finally, summarize evaluate emerging treatments potential initiatives aimed at managing

Language: Английский

Citations

2
Forkhead box D subfamily genes in colorectal cancer: potential biomarkers and therapeutic targets DOI Creative Commons
Ying Chen,

Haiyan Qiao,

Ruiqi Zhong

et al.

PeerJ, Journal Year: 2024, Volume and Issue: 12, P. e18406 - e18406

Published: Oct. 29, 2024

The forkhead box (FOX) family members regulate gene transcription and expression. FOX various biological processes, such as cell proliferation tumorigenesis. FOXD, a protein subfamily, is associated with poor prognosis for cancers. However, the potential clinical value of FOXD subfamily in colorectal cancer (CRC) has not yet been elucidated. Therefore, this study, we aimed to determine role CRC development.

Language: Английский

Citations

1
Epigenetic modifications associated to diabetic peripheral neuropathic pain (Review) DOI Creative Commons
Tianle Gao,

Jingya Luo,

Jie Fan

et al.

Molecular Medicine Reports, Journal Year: 2024, Volume and Issue: 31(1)

Published: Nov. 13, 2024

The present review aimed to provide an update on the scientific progress of role epigenetic modifications diabetic peripheral neuropathic pain (DPNP). DPNP is a devastating and troublesome complication diabetes mellitus (DM), which affects one third patients with DM causes severe hyperalgesia allodynia, leading challenges in treatment these patients. pathophysiology multifactorial not yet fully understood options for this disease are currently unsatisfactory. underlying mechanisms have largely been explored animal models mechanism‑derived approach might offer potential therapeutic‑target attenuating certain phenotypes DPNP. Altered gene expression levels within or central nervous systems (CNS) crucial mechanism DPNP, however, transcriptional genes elucidated. Epigenetic modifications, such as DNA methylation histone (methylation, acetylation, phosphorylation), can alter via chromatin remodeling. Moreover, it has reported that altering CNS, contributes changes both sensitivity pharmacological efficacy Therefore, summarized findings relevant literature alterations therapeutic targeting future disease.

Language: Английский

Citations

1
N6‐Methyladenosine Modification on the Function of Female Reproductive Development and Related Diseases DOI Creative Commons
Xiangrong Cui, Huihui Li,

Xia Huang

et al.

Immunity Inflammation and Disease, Journal Year: 2024, Volume and Issue: 12(12)

Published: Dec. 1, 2024

N6-methyladenosine (m6A) modification is a widespread and reversible epigenetic alteration in eukaryotic mRNA, playing pivotal role various biological functions. Its significance female reproductive development associated diseases has recently become focal point of research.

Language: Английский

Citations

1
Ferroptosis Regulated by 5-HT3a Receptor via Calcium/Calmodulin Signaling Contributes to Neuropathic Pain in Brachial Plexus Avulsion Rat Models DOI
C.S. Liao, Jinding Guo, Shenqian Li

et al.

ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 6, 2024

Neuropathic pain is a prevalent complication following brachial plexus avulsion (BPA). Ferroptosis has been implicated in various nervous system disorders. However, the association between ferroptosis and neuropathic induced by BPA remains unclear. This study aimed to investigate role of BPA-induced pain. A rat model was established via induction. Pain thresholds rats were measured after surgery intraperitoneal injection Fer-1. On day 14 postsurgery, spinal dorsal horn (SDH) samples collected for Western blotting, biochemical analysis, immunohistochemistry analyze expression distribution ferroptosis-related markers. The relationships among 5-HT3a receptor, calcium/calmodulin (CaM) pathway, assessed lipid peroxidation assays, including iron calcium content, reactive oxygen species, glutathione peroxidase 4 (GPX4), ACSL, CaM expression. associated with accumulation, increased peroxidation, dysregulated Acyl-CoA synthetase long-chain family member 4, GPX4, changes transferrin divalent metal transporter 1, ferroportin-1 (FPN1). Intraperitoneal administration Fer-1 reversed all these alterations mitigated mechanical cold hypersensitivity. Inhibition receptor reduced extent ferroptosis. Furthermore, can regulate calcium/CaM pathway L-type channels (LTCCs), blocking LTCCs nifedipine also alleviated SDH rats. Taken together, BPA, development involves ferroptosis, which regulated through signaling SDH.

Language: Английский

Citations

0
H3K27 trimethylation-mediated downregulation of miR-216a-3p in sensory neurons regulates neuropathic pain behaviors via targeting STIM1 DOI
Yufang Sun, Tao Yu, Junping Cao

et al.

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 45(1), P. e0607242024 - e0607242024

Published: Nov. 26, 2024

Although the therapeutic potential of microRNA-mediated gene regulation has been investigated, its precise functional regulatory mechanism in neuropathic pain remains incompletely understood. In this study, we elucidate that miR-216a-3p serves as a critical noncoding RNA involved modulation trigeminal-mediated pain. By conducting RNA-seq and qPCR analysis, observed notable decrease injured trigeminal ganglia (TG) male rats. Intra-TG administration agomir or lentiviral-mediated overexpression specifically sensory neurons TGs alleviated established behaviors, while downregulation (pharmacologically genetically) naive rats induced behaviors. Moreover, nerve injury significantly elevated histone H3 lysine-27 (H3K27) trimethylation (H3K27me3) levels ipsilateral TG, thereby suppressing SRY-box TF 10 (SOX10) binding to promoter resulting reduction miR-216a-3p. Inhibiting enzymes responsible for catalyzing H3K27me3 restored injury-induced expression markedly ameliorated Furthermore, targeted stromal interaction molecule 1 (STIM1), decreased associated with caused significant upregulation protein abundance STIM1. Conversely, TG suppressed STIM1 reversed mechanical allodynia. Together, mechanistic understanding H3K27me3-dependent SOX10/miR-216a-3p/STIM1 signaling axial may facilitate discovery innovative strategies management.

Language: Английский

Citations

0