Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ALKBH5 Demethylates the m6A Modification of SOCS3 in Microglia/Macrophages and Alleviates Neuroinflammation after Brain Injury

ABSTRACT: ALKBH5 Demethylates the m6A Modification of SOCS3 in Microglia/Macrophages and Alleviates Neuroinflammation after Brain Injury

PROVIDER: PRJNA1292149 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

ALKBH5 Demethylates the m6A Modification of SOCS3 in Microglia/Macrophages and Alleviates Neuroinflammation after Brain Injury [scRNA-seq]

Project description:Microglia/macrophage-induced neuroinflammation plays a crucial role in the progression of traumatic brain injury (TBI). However, the involvement of N6-methyladenosine (m6A) RNA modifications in this process remains elusive. Single-cell RNA sequencing (scRNA-seq) and m6A RNA immunoprecipitation sequencing (MeRIP-seq) across multiple time points post-injury revealed a strong correlation between m6A modifications and genes enriched in microglia/macrophage. Furthermore, the m6A demethylase ALKBH5 was identified as a key regulator of dynamic m6A patterns at the injury site. ALKBH5 suppression in microglia/macrophage exacerbated neuroinflammation in vitro and worsened neurological deficits in controlled cortical impact (CCI) models. MeRIP-qPCR and RNA pull-down assays revealed SOCS3 was a downstream target of ALKBH5-mediated m6A demethylation. This demethylation stabilized Socs3 mRNA and enhanced its protein expression, which in turn suppressed neuroinflammation via inhibiting the JAK2-STAT3 pathway. Conversely, SOCS3 depletion impaired functional recovery after injury. These findings unveiled a critical ALKBH5-m6A-SOCS3 regulatory axis that mitigated microglia/macrophage-driven neuroinflammation after TBI, underscoring its potential as a therapeutic intervention target for TBI progression.

2025-09-05 | GSE302863 | GEO

ALKBH5 Demethylates the m6A Modification of SOCS3 in Microglia/Macrophages and Alleviates Neuroinflammation after Brain Injury

Project description:Microglia/macrophage_induced neuroinflammation plays a crucial role in the progression of traumatic brain injury (TBI). However, the involvement of N6_methyladenosine (m6A) RNA modifications in this process remains elusive. Single_cell RNA sequencing (scRNA_seq) and m6A RNA immunoprecipitation sequencing (MeRIP_seq) across multiple time points post_injury revealed a strong correlation between m6A modifications and genes enriched in microglia/macrophage. Furthermore, the m6A demethylase ALKBH5 was identified as a key regulator of dynamic m6A patterns at the injury site. ALKBH5 suppression in microglia/macrophage exacerbated neuroinflammation in vitro and worsened neurological deficits in controlled cortical impact (CCI) models. MeRIP_qPCR and RNA pull_down assays revealed SOCS3 was a downstream target of ALKBH5_mediated m6A demethylation. This demethylation stabilized Socs3 mRNA and enhanced its protein expression, which in turn suppressed neuroinflammation via inhibiting the JAK2_STAT3 pathway. Conversely, SOCS3 depletion impaired functional recovery after injury. These findings unveiled a critical ALKBH5_m6A_SOCS3 regulatory axis that mitigated microglia/macrophage_driven neuroinflammation after TBI, underscoring its potential as a therapeutic intervention target for TBI progression.

2025-09-05 | GSE302776 | GEO

ALKBH5 Demethylates the m6A Modification of SOCS3 in Microglia/Macrophages and Alleviates Neuroinflammation after Brain Injury [scRNA-seq]

Project description:ALKBH5 Demethylates the m6A Modification of SOCS3 in Microglia/Macrophages and Alleviates Neuroinflammation after Brain Injury [scRNA-seq]

| PRJNA1292715 | ENA

Photobiomodulation mitigates LPS-induced astrocyte neuroinflammation via the STAT5A/SOCS3 axis

Project description:Neuroinflammation plays an important role in the occurrence and development of neurological diseases. In addition to microglia, the role of astrocytes in neuroinflammation has gradually attracted attention. Photobiomodulation (PBM), as a non-invasive, safe and effective treatment, has been shown to alleviate neuroinflammation and show potential in improving astrocyte activation. In this study, by analyzing the effects at different times, the spatiotemporal regulation and molecular mechanism of PBM on astrocytes were deeply explored. The results showed that PBM significantly attenuated LPS-induced upregulation of inflammatory factors and mitochondrial dysfunction in astrocytes under LPS stimulation for 4 hours and 24 hours. RNA-seq analysis showed that the JAK-STAT pathway played an important role in the early stage of astrocyte inflammatory response. PBM can promote the expression of Socs3 by activating Stat5a translocation to the nucleus, further inhibit the overactivation of the JAK-STAT inflammatory signaling pathway, and thus alleviate astrocyte inflammation. Taken together, this study provides new insights into the molecular mechanism of the potential application of PBM in the treatment of neuroinflammation.

2025-10-31 | GSE300419 | GEO

ALKBH5 cooperated with LINC00659 promote gastric cancer progression by JAK1 mRNA m6A-YTHDF2-dependent modification [2-m6A]

Project description:N6-methyladenosine (m6A) modification is the most prevalent RNA epigenetic regulation in eukaryotic cells. Recent studies focused on the association between m6A and non-coding RNAs. The demethylase ALKBH5 acts as critical oncogenes or tumor suppressors through multiple mechanisms in various cancers. Here, we find that ALKBH5 is highly expressed in GC tissues and is associated with poor prognosis. ALKBH5 promoted the proliferation and metastasis both in vitro and in vivo. ALKBH5 was recruited by LINC00659, which removed m6A modifications of JAK1, leading to the upregulated expression of JAK1.Since ALKBH5 and LINC00659 have oncogenic role in gastric cancer (GC) progression with poor prognosis, ALKBH5-LINC00659/m6A/JAK1 axis can be new biological mechanisms behind GC development and future therapeutic opportunities.

2024-08-17 | GSE182542 | GEO

Protein kinase A regulates ferroptosis by controlling GPX4 m6A modification through phosphorylation of ALKBH5

Project description:GPX4-dependent ferroptosis has emerged as a therapeutic strategy for cancer treatment. Here, we demonstrated that protein kinase A (PKA) participates in the regulation of ferroptosis by controlling the m6A modification of GPX4 in an ALKBH5-dependent manner. Notably, we identified ALKBH5, an m6A demethylase, as a novel target of PKA, which drives phosphorylation-dependent degradation of ALKBH5 protein. Moreover, the deletion of ALKBH5 represses ferroptotic cell death by maintaining GPX4 m6A modification and stability. Thus, by regulating ALKBH5-dependent GPX4 stability, PKA acts as a key regulator of ferroptosis. Our study unveils the involvement of PKA in m6A modification, which could control GPX4-dependent ferroptosis and tumor progression.

2025-12-09 | GSE283869 | GEO

Post-translational Modification of RNA m6A Demethylase ALKBH5 Regulates ROS-induced DNA Damage Response

Project description:Faithful genome integrity maintenance plays an essential role in cell survival. Here, we identify the RNA demethylase ALKBH5 as a key regulator that protects cells from DNA damage and apoptosis during reactive oxygen species (ROS)-induced stress. We find that ROS significantly induces global mRNA N6-methyladenosine (m6A) levels by modulating ALKBH5 post-translational modifications (PTMs), leading to the rapid and efficient induction of thousands of genes involved in a variety of biological processes including DNA damage repair. Mechanistically, ROS promotes ALKBH5 SUMOylation through activating ERK/JNK signaling, leading to inhibition of ALKBH5 m6A demethylase activity by blocking substrate accessibility. Moreover, ERK/JNK/ALKBH5-PTMs/m6A axis is activated by ROS in hematopoietic stem/progenitor cells (HSPCs) in vivo in mice, suggesting a physiological role of this molecular pathway in the maintenance of genome stability in HSPCs. Together, our study uncovers a molecular mechanism involving ALKBH5 PTMs and increased mRNA m6A levels that protect genomic integrity of cells in response to ROS.

2021-04-29 | GSE144620 | GEO

ALKBH5 cooperated with LINC00659 promote gastric cancer progression by JAK1 mRNA m6A-YTHDF2-dependent modification

2024-08-17 | GSE182544 | GEO

ALKBH5 cooperated with LINC00659 promote gastric cancer progression by JAK1 mRNA m6A-YTHDF2-dependent modification [polyA]

2024-08-17 | GSE182543 | GEO

Photobiomodulation mitigates LPS-induced astrocyte neuroinflammation via the STAT5A/SOCS3 axis

Project description:Photobiomodulation mitigates LPS-induced astrocyte neuroinflammation via the STAT5A/SOCS3 axis

| PRJNA1280916 | ENA