ArticleJournal of experimental & clinical cancer research : CR2023
GABA induced by sleep deprivation promotes the proliferation and migration of colon tumors through miR-223-3p endogenous pathway and exosome pathway.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 54 citations in OpenAlex.
- Ubiquitin signaling in tumor-associated macrophage reprogramming: mechanisms and therapeutic opportunities in cancers.Biomarker research · 2026Review
- Integrative multi-omics profiling of insomnia-related molecular features reveals microbiome, immune, and therapy-relevant heterogeneity in colorectal cancer.Microbiology spectrum · 2026Article
- Neural regulation in lung cancer: from mechanisms to new therapeutic perspectives.Clinical and experimental medicine · 2026Review
- A malignant symbiosis: The neuro-metabolic symphony rewires the tumor microenvironment.Neoplasia (New York, N.Y.) · 2026Review
- Abnormally Elevated PKCδ Delays Diabetic Wound Healing by Inhibiting the GAD1-GABA Pathway.Diabetes & metabolism journal · 2026Article
- CD4 + T cell-derived exosomal miR-223-3p serves as a potential biomarker for systemic lupus erythematosus and attenuates lupus nephritis in NZBWF1/J mice.Journal of nanobiotechnology · 2026Article
- AQP1 is Involved in NLRP3-Related Microglial Polarization and Cognitive Impairment in Chronic Sleep Deprivation.Inflammation · 2026Article
- Diagnostic Potential of Exosomes in Colorectal Cancer: Current Advances and Future Perspectives.Molecules (Basel, Switzerland) · 2026Review
- miR-223-3p improves macrophage polarization balance and mitochondrial metabolism to ameliorate uveitis by orchestrating P65Cellular & molecular biology letters · 2026Article
- Microbial influences on immune modulation and colorectal cancer progression through combined transcriptomic and microbiomic analysis.iMetaOmics · 2026Article
- Charting the expression landscape of human long non-coding RNAs across diverse biological contexts with LncExpDB 2.0.Nucleic acids research · 2026Article
- Sleep disturbances promote colorectal cancer perineural invasion via GABA-mediated BDNF secretion.American journal of cancer research · 2026Article
- Sleep Deprivation Promotes Colorectal Cancer in ApcInternational journal of biological sciences · 2026Article
- Peripheral Nerve-Cancer Interactions in the Tumor Microenvironment: A Three-Dimensional Framework Integrating Mechanisms, Modulators, and Therapeutic Strategies.Research (Washington, D.C.) · 2026Review
- Exosomal miR-223-3p from mesenchymal stem cells targets FBXW7 to inhibit intervertebral disc degeneration: mechanism insights.Journal of orthopaedic surgery and research · 2025Article
- Extracellular vesicles cargo orchestration in colorectal cancer: immune evasion, stromal remodeling, and therapeutic frontiers.Molecular cancer · 2025Review
- Neurotransmitters and Immunity: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets.MedComm · 2025Review
- Advances in Tumor-Derived Exosomal Non-Coding RNAs Regulating M2 Macrophage Polarization: Molecular Mechanisms and Signaling Pathway.Cancer medicine · 2025Review
- Neurotransmitters in tumors: chemical cross-talk shaping tumor progression.Biomarker research · 2025Review
- Exosomal transfer of miR-223-3p from carcinoma-associated fibroblasts promotes the malignant properties and chemoresistance of colon cancer cells by targeting NF2/Hippo signaling.Medical oncology (Northwood, London, England) · 2025Article
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundResearch has indicated that long-term sleep deprivation can lead to immune dysfunction and participate in the occurance and progression of tumors. However, the relationship between sleep deprivation and colon cancer remains unclear. This study explored the specific mechanism through which sleep deprivation promotes the proliferation and migration of colon cancer, with a focus on the neurotransmitter GABA.
methodsChronic sleep deprivation mice model were used to investigate the effect of sleep disorder on tumors. We detected neurotransmitter levels in the peripheral blood of mice using ELISA. CCK-8 assay, colony formation assay, wound healing assay, and transwell assay were performed to investigate the effect of GABA on colon cancer cells, while immunofluorescence showed the distribution of macrophages in lung metastatic tissues. We isolated exosomes from a GABA-induced culture medium to explore the effects of GABA-induced colon cancer cells on macrophages. Gain- and loss-of-function experiments, luciferase report analysis, immunohistochemistry, and cytokine detection were performed to reveal the crosstalk between colon cancer cells and macrophages.
resultsSleep deprivation promote peripheral blood GABA level and colon cancer cell proliferation and migration. Immunofluorescence analysis revealed that GABA-induced colon cancer metastasis is associated with enhanced recruitment of macrophages in the lungs. The co-culture results showed that GABA intensified M2 polarization of macrophage induced by colon cancer cells. This effect is due to the activation of the macrophage MAPK pathway by tumor-derived exosomal miR-223-3p. Furthermore, M2-like macrophages promote tumor proliferation and migration by secreting IL-17. We also identified an endogenous miR-223-3p downregulation of the E3 ligase CBLB, which enhances the stability of cMYC protein and augments colon cancer cells proliferation and migration ability. Notably, cMYC acts as a transcription factor and can also regulate the expression of miR-223-3p.
conclusionOur results suggest that sleep deprivation can promote the expression of miR-223-3p in colon cancer cells through GABA, leading to downregulation of the E3 ligase CBLB and inhibition of cMYC ubiquitination. Simultaneously, extracellular miR-223-3p promotes M2-like macrophage polarization, which leads to the secretion of IL-17, further enhancing the proliferation and migration of colon cancer cells.
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