Wnt3a/YTHDF1 Regulated Oxaliplatin-Induced Neuropathic Pain Via TNF-α/IL-18 Expression in the Spinal Cord

Xiu-juan, Bai; Huang, Yongtian; Huang, Wan; Zhang, Yingjun; Zhang, Kun; Li, Yujuan; Ouyang, Handong

doi:10.1007/s10571-022-01267-8

Cited by 13 publications

(11 citation statements)

References 53 publications

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“…Utilizing m6A-seq, proteomics, and polysome profiling, the authors showed that YTHDF1 promotes the translation of m6A-modified autophagy-related genes (ATG)-2A and ATG14, thus facilitating the induction of autophagy in HCC cells [55]. Wnt3a induces YTHF1 over-expression and promotes oxaliplatin-induced neuropathic pain in mice [56]. In colorectal cancer, the oncogenic transcription factor c-Myc promotes the expression of YTHDF1 and plays a significant role in colorectal cancer progression [57].…”

Section: Ythdf1 Is Regulated At Multi-levelsmentioning

confidence: 99%

The function and clinical implication of YTHDF1 in the human system development and cancer

Ren

Yuan

et al. 2023

Biomark Res

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YTHDF1 is a well-characterized m6A reader protein that is essential for protein translation, stem cell self-renewal, and embryonic development. YTHDF1 regulates target gene expression by diverse molecular mechanisms, such as promoting protein translation or modulating the stability of mRNA. The cellular levels of YTHDF1 are precisely regulated by a complicated transcriptional, post-transcriptional, and post-translational network. Very solid evidence supports the pivotal role of YTHDF1 in embryonic development and human cancer progression. In this review, we discuss how YTHDF1 influences both the physiological and pathological biology of the central nervous, reproductive and immune systems. Therefore we focus on some relevant aspects of the regulatory role played by YTHDF1 as gene expression, complex cell networking: stem cell self-renewal, embryonic development, and human cancers progression. We propose that YTHDF1 is a promising future cancer biomarker for detection, progression, and prognosis. Targeting YTHDF1 holds therapeutic potential, as the overexpression of YTHDF1 is associated with tumor resistance to chemotherapy and immunotherapy.

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Section: Ythdf1 Is Regulated At Multi-levelsmentioning

confidence: 99%

The function and clinical implication of YTHDF1 in the human system development and cancer

Ren

Yuan

et al. 2023

Biomark Res

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“…Treatment approaches include sodium channel blockers and targeting the Wnt3a/YTHDF1 pathway. Numerous genes, such as GSTPI, SCNA, KCNN3, ABCC2, AGXT, and others, are associated with OXAIPN, while sodium channel-related genes like SCN4A, SCN10A, and SCN9A, as well as proteins like OCT2, Caspase-3, GAP43, and pNfH, are linked to this condition, providing insights into its genetic and molecular underpinnings (31,32). Its effects on the action potential’s duration, the sodium current’s peak, voltage–response relationship, inactivation current, and sensitivity to tetrodotoxin (TTX) (33).…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: The Molecular Signature Associated with Oxaliplatin Induced Peripheral Neuropathy in Colorectal Cancer

Modekurty

2024

Preprint

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Background: Oxaliplatin is the standard treatment option for colorectal cancer (CRC) which is one of the most prevalent forms of cancer. However, patients suffer either treatment discontinuation or adverse post-treatment life quality due to Oxaliplatin-induced peripheral neuropathy. Methods: Our study has comprehensively explored the molecular mechanisms underlying Oxaliplatin-induced peripheral neuropathy via an extensive literature survey and identified multiple genes that may contribute to neuropathy and neurotoxicity. In addition to that, the publicly available bulk transcriptomic data of Illumina HiSeq 2500 platform, comprising the CRC tissue of 18 individuals' tumor and adjacent normal tissue was processed to identify differentially expressed genes (DEGs). Moreover, the single-cell RNA sequencing data of 10X genomics comprising normal and tumor tissues was subjected to analysis using Seurat and sctype R packages to uncover the cancer cells associated DEGs. Functional and pathway enrichment analysis was conducted using the Genecodis4 web-based tool. Next, RNA-seq data of CRC cell lines treated with Oxaliplatin compared with normal individuals, was also processed and DEGs were determined to validate the inhibition of a curated list of neuropathy-associated genes. Results: From literature and database searches, a total of 1367 genes, including ion channel genes, normal sensory neuron-associated genes, and axon-excitability-related genes were collected that are either reported to be or may be contributing to neuropathy among cancer survivors upon oxaliplatin administration. The bulk transcriptomic data analysis revealed 715 DEGs and single-cell analysis uncovered 2,854 DEGs. Identified upregulated genes from single-cell data analysis, such as LGALS4, SPINK4, TFF3, REG4, and REG1A were found to be associated with tumor proliferation via epithelial-mesenchymal transitions, oxidative stress, dysregulated immune system, and inflammation which can be utilized as potential targets to devise novel therapeutic strategies for CRC treatment. Furthermore, many proteins involved in axon-excitability (NGF, SOD1, ROBO1, CNTNAP2, CNTNAP2, and KCNMB1), normal sensory neuron (SOX10, APOE, SST, S1PR1, and KCND3), voltage-gated sodium (SCNN1B, SCNN1G, SCNN1A, SCN1B, and SCN2B), calcium (CACNA2D2, CACNA1A, CACNA1C, CACNA1E, and CACNA1F), and potassium channels (KCND3, KCNMB1, KCNMA1, KCNJ2, and KCNN4) showed downregulation due to the oxaliplatin administration in CRC cell lines and their inhibition may have led to neuropathy which needs further validations. Conclusion: Our study uncovers the downregulation of multiple genes upon oxaliplatin administration leading to neuropathy development and also elucidates potential therapeutic targets for better prognosis of CRC.

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“…In the context of chronic pain, the interaction between neurons, astrocytes, and microglial cells may be mediated by the activated cytokine and chemokine signaling pathways. Oxaliplatin can induce the production of certain pro-inflammatory cytokines in SC cells, including IL-18, TNF-α, and MMP2 ( Huang et al, 2021 ; Bai et al, 2023 ). These cytokines can bind to their respective receptors, enhancing glutamate activity and inhibiting inhibitory synaptic transmission, leading to increased excitability of neurons in the SC and subsequently chronic pain ( Liu et al, 2017 ; Zhang et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Tetrandrine alleviates oxaliplatin-induced mechanical allodynia via modulation of inflammation-related genes

Zhang,

Wu,

Liu

et al. 2024

Front. Mol. Neurosci.

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Oxaliplatin, a platinum-based chemotherapy drug, causes neuropathic pain, yet effective pharmacological treatments are lacking. Previously, we showed that tetrandrine (TET), with anti-inflammatory properties, reduces mechanical allodynia in nerve-injured mice. This study explores the effect of TET on oxaliplatin-induced mechanical allodynia and gene changes in mice. Male C57BL/6J mice received oxaliplatin intraperitoneally to induce mechanical allodynia. Post-treatment with TET or vehicle, the mechanical withdrawal threshold (WMT) was assessed using von Frey filaments. TET alleviated oxaliplatin-induced mechanical allodynia. RNA sequencing identified 365 differentially expressed genes (DEGs) in the Control vs. Oxaliplatin group and 229 DEGs in the Oxaliplatin vs. TET group. Pearson correlation analysis of co-regulated DEGs and inflammation-related genes (IRGs) revealed 104 co-regulated inflammation-related genes (Co-IRGs) (|cor| > 0.8, P < 0.01). The top 30 genes in the PPI network were identified. Arg2, Cxcl12, H2-Q6, Kdr, and Nfkbia were highlighted based on ROC analysis. Subsequently, Arg2, Cxcl12, Kdr, and Nfkbia were further verified by qRCR. Immune infiltration analysis indicated increased follicular CD4 T cell infiltration in oxaliplatin-treated mice, reduced by TET. Molecular docking showed strong binding affinity between TET and proteins encoded by Arg2, Cxcl12, Kdr, and Nfkbia. In summary, TET may alleviate oxaliplatin-induced peripheral neuropathy in clinical conditions.

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Wnt3a/YTHDF1 Regulated Oxaliplatin-Induced Neuropathic Pain Via TNF-α/IL-18 Expression in the Spinal Cord

Cited by 13 publications

References 53 publications

The function and clinical implication of YTHDF1 in the human system development and cancer

The function and clinical implication of YTHDF1 in the human system development and cancer

WITHDRAWN: The Molecular Signature Associated with Oxaliplatin Induced Peripheral Neuropathy in Colorectal Cancer

Tetrandrine alleviates oxaliplatin-induced mechanical allodynia via modulation of inflammation-related genes

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