Methyltransferase-like 3 contributes to inflammatory pain by targeting TET1 in YTHDF2-dependent manner

Pan, Zengxiang; Zhang, Qi; Liu, Xiaodan; Zhou, Huimin; Jin, Tong; Hao, Lü; Xie, Ling; Zhang, Ming; Yang, Xiao-Xiao; Sun, Meng-Lan; Xue, Zhou-Ya; Yang, Tao; Ye, Xinchun; Shen, Wen; Cao, Jun-Li

doi:10.1097/j.pain.0000000000002218

Cited by 38 publications

(36 citation statements)

References 70 publications

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“…At present, a large number of studies have shown that m 6 A modifications caused by the abnormal expression of m 6 A core modification and reading proteins are involved in various physiological and pathological processes, such as biological growth and development, sperm development and maturation, DNA damage repair, biological rhythms, and various types of tumors [ 33 , 46 ]. Chai et al showed that YTHDF2 could promote the malignant progression of gliomas by accelerating UBX domain protein 1 (UBXN1) mRNA degradation via METTL3-mediated m 6 A modification [ 1 ]; Pan et al verified that YTHDF2 could lead to the reduction of Tet1 mRNA decay by binding to m 6 A in Tet1 mRNA [ 47 ]; Hou et al confirmed that the small ubiquitin-related modifier (SUMO)ylation of YTHDF2 could significantly increase the binding affinity of m 6 A-modified mRNAs and subsequently result in deregulated gene expression responsible for cancer progression [ 48 ]. We speculated that METTL14 might repress ASS1 mRNA stability via an m 6 A-YTHDF2-dependent pathway.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: N(6)-adenosine-methyltransferase-14 promotes glioma tumorigenesis by repressing argininosuccinate synthase 1 expression in an m6A-dependent manner

et al. 2022

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Glioma is one of the leading causes of tumor-related deaths worldwide, but its potential mechanism remains unclear. This study aimed to explore the biological role and potential mechanism of argininosuccinate synthase 1 (ASS1) in glioma. The relative expression levels of ASS1 in glioma specimens and cell lines were calculated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. The biological functions of ASS1 were demonstrated using the 5-ethynyl-2ʹ-deoxyuridine (EdU) assay, transwell assay, and in vivo experiments. In addition, methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), and luciferase reporter assays were performed to explore the molecular mechanism of ASS1 in glioma. ASS1 expression levels were found to be downregulated in glioma specimens and cell lines. Functionally, we confirmed that ASS1 inhibited glioma cell proliferation, migration, invasion, and growth both. Furthermore, we found that ASS1 was a target of N(6)-adenosine-methyltransferase-14 (METTL14)-mediated N 6 -methyladenosine (m 6 A) modification. Overexpression of METTL14 markedly elevated ASS1 mRNA m 6 A modification and suppressed ASS1 mRNA expression. We also revealed that METTL14-mediated ASS1 mRNA degradation relied on the YTH m6A RNA-binding protein 2 (YTHDF2)-dependent pathway. We confirmed that decreased ASS1 expression promoted the cell proliferation, migration, and invasion in glioma, and that the METTL14/ASS1/YTHDF2 regulatory axis may be an effective therapeutic target for glioma.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: N(6)-adenosine-methyltransferase-14 promotes glioma tumorigenesis by repressing argininosuccinate synthase 1 expression in an m6A-dependent manner

et al. 2022

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“…RNA extraction and qRT-PCR. RNA extraction and qRT-PCR were performed as described previously (Pan et al, 2021). In brief, total RNA was extracted using RNAiso Plus protocol (catalog #9109, Takara) and reversely transcribed into cDNA using HiScriot II Reverse Transcriptase (catalog # R223-1, Vazyme).…”

Section: Methodsmentioning

confidence: 99%

The Slack Channel Regulates Anxiety-Like Behaviors via Basolateral Amygdala Glutamatergic Projections to Ventral Hippocampus

et al. 2022

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Anxiety disorders are a series of mental disorders characterized by anxiety and fear, but the molecular basis of these disorders remains unclear. In the present study, we find that the global Slack KO male mice exhibit anxious behaviors, whereas the Slack Y777H male mice manifest anxiolytic behaviors. The expression of Slack channels is rich in basolateral amygdala (BLA) glutamatergic neurons and downregulated in chronic corticosterone-treated mice. In addition, electrophysiological data show enhanced excitability of BLA glutamatergic neurons in the Slack KO mice and decreased excitability of these neurons in the Slack Y777H mice. Furthermore, the Slack channel deletion in BLA glutamatergic neurons is sufficient to result in enhanced avoidance behaviors, whereas Kcnt1 gene expression in the BLA or BLA-ventral hippocampus (vHPC) glutamatergic projections reverses anxious behaviors of the Slack KO mice. Our study identifies the role of the Slack channel in controlling anxious behaviors by decreasing the excitability of BLA-vHPC glutamatergic projections, providing a potential target for anxiolytic therapies.

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“…Inflammatory pain is evoked by inflammation-associated stimuli and is often established in animal models using wound incision or injection of inflammatory chemical irritants, such as complete Freund’s adjuvant (CFA), carrageenan or lipopolysaccharides (LPS) ( Pan et al, 2021 ). Recent literatures have demonstrated that intraplantar administration of complete Freund’s adjuvant (CFA) or ceramide not only down-regulates paw withdrawal mechanical threshold and paw withdrawal thermal latency, but also up-regulates the expression of the NOD-like receptor protein 2 (NLRP2)/caspase-1/IL-1β in small-sized DRG primary sensory neurons and the generation of NLRP3/caspase-1 in spinal dorsal horn neurons ( Matsuoka et al, 2019 ; Hua et al, 2022 ).…”

Section: Caspases and Inflammatory Painmentioning

confidence: 99%

The Involvement of Caspases in Neuroinflammation and Neuronal Apoptosis in Chronic Pain and Potential Therapeutic Targets

Zhang

et al. 2022

Front. Pharmacol.

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Chronic pain is a common, complex and unpleasant sensation following nerve injury, tissue trauma, inflammatory diseases, infection and cancer. It affects up to 25% of adults and is increasingly recognized as the leading cause of distress, disability and disease burden globally. Chronic pain is often refractory to most current analgesics, thus emphasizing the requirement for improved therapeutic medications. It is of great importance to elucidate the specific pathogenesis of chronic pain with different etiologies. Recent progress has advanced our understanding in the contribution of neuroinflammation and glial cells (microglia and astrocyte) activation in the plasticity of excitatory nociceptive synapses and the development of chronic pain phenotypes. Oxidative stress-associated neuronal apoptosis is also identified to be a pivotal step for central pain sensitization. The family of cysteine aspartate specific proteases (Caspases) has been well known to be key signaling molecules for inflammation and apoptosis in several neurological conditions. Recent studies have highlighted the unconventional and emerging role of caspases in microgliosis, astrocytes morphogenesis, chemokines release, cytokines secretion and neuronal apoptosis in initiating and maintaining synaptogenesis, synaptic strength and signal transduction in persistent pain hypersensitivity, suggesting the possibility of targeting caspases pathway for prevention and treatment of chronic pain. In this review, we will discuss and summarize the advances in the distinctive properties of caspases family in the pathophysiology of chronic pain, especially in neuropathic pain, inflammatory pain, cancer pain and musculoskeletal pain, with the aim to find the promising therapeutic candidates for the resolution of chronic pain to better manage patients undergoing chronic pain in clinics.

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Methyltransferase-like 3 contributes to inflammatory pain by targeting TET1 in YTHDF2-dependent manner

Abstract: Relative mRNA level ** 0d 2h 1d 3d 7d Time after CFA injection Mettl14 0.0 0.5

Cited by 38 publications

References 70 publications

RETRACTED ARTICLE: N(6)-adenosine-methyltransferase-14 promotes glioma tumorigenesis by repressing argininosuccinate synthase 1 expression in an m6A-dependent manner

RETRACTED ARTICLE: N(6)-adenosine-methyltransferase-14 promotes glioma tumorigenesis by repressing argininosuccinate synthase 1 expression in an m6A-dependent manner

The Slack Channel Regulates Anxiety-Like Behaviors via Basolateral Amygdala Glutamatergic Projections to Ventral Hippocampus

The Involvement of Caspases in Neuroinflammation and Neuronal Apoptosis in Chronic Pain and Potential Therapeutic Targets

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