ArticleCell death & disease2023
FOXO1 regulates Th17 cell-mediated hepatocellular carcinoma recurrence after hepatic ischemia-reperfusion injury.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 34 citations in OpenAlex.
- Rhoifolin Alleviates Ulcerative Colitis by Targeting NMNAT1 and Activating SIRT1-FOXO1 Signaling to Enhance ILC3s Effector Function.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- FOXO family and neurodegenerative diseases: Mechanisms of action and therapeutic potential.Redox biology · 2026Review
- SAA/FPR2 Signaling Between Pericentral Hepatocytes and Macrophages Exacerbates Zonated Liver Transplant Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Redefining Liver Transplantation Indications for Hepatic Malignancies in the Era of Precision Transplant Oncology: An Up-to-Date Narrative Review.Journal of clinical medicine · 2026Review
- TLR4 maintains Treg-mediated protection against adverse outcomes in a model of hepatic surgical stress.The Journal of clinical investigation · 2026Article
- BMSC-derived exosomes facilitate osteogenesis and ameliorate ageing-related bone loss through restoring Th17/Treg homeostasis via the miR-21/Skp2/FoxO1 axis.Stem cell research & therapy · 2026Article
- The Role of CD4Cells · 2026Review
- Machine learning-based prognostic model of stemness and angiogenesis-related genes for predicting prognosis and immune infiltration in patients with HCC.Scientific reports · 2026Article
- Nuclear receptor corepressor 1 is a potential diagnostic and prognostic biomarker in clear cell renal cell carcinoma.Scientific reports · 2026Article
- Single-cell dissection of hepatocellular carcinoma immunity: from heterogeneous subtypes to precision therapeutics.Frontiers in immunology · 2026Review
- Six-Transmembrane Epithelial Antigen of the Prostate 1 Promotes HCC Proliferation and Metastasis in vitro and in vivo via the Wnt/β-Catenin Signaling Pathway.Cancer management and research · 2026Article
- Emerging nanomedicine for liver diseases treatment.Journal of nanobiotechnology · 2025Review
- miR-184 in hepatocellular carcinoma: a promising therapeutic target.Journal of physiology and biochemistry · 2025Review
- ANXA2 in hepatocellular carcinoma: orchestrating tumorigenesis, progression, and therapeutic resistance toward precision targeting.Journal of translational medicine · 2025Review
- Constructing biomimetic microenvironments for liver regeneration.Journal of nanobiotechnology · 2025Review
- Immune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy.Cellular & molecular immunology · 2025Review
- DNMT1 recruits RUNX1 and represses FOXO1 transcription to inhibit anti-inflammatory activity of regulatory T cells and augments sepsis-induced lung injury.Cell biology and toxicology · 2025Article
- Hepatocyte FoxO1 depletion exacerbates hepatic inflammation in MASH by targeting cystathionine γ-lyase.Scientific reports · 2025Article
- The roles of Cryptochrome-1: the circadian clock as a control point in cancer therapy.Journal of translational medicine · 2025Review
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Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatic ischemia-reperfusion injury (IRI) is considered as an effecting factor for hepatocellular carcinoma (HCC) recurrence. Th17/Treg cells are a pair of essential components in adaptive immune response in liver IRI, and forkhead box O1 (FOXO1) has the properties of maintaining the function and phenotype of immune cells. Herein, we illuminated the correlation and function between Th17/Treg cell balance and FOXO1 in IRI-induced HCC recurrence.
methodsRNA sequencing was performed on naive CD4+ T cells from normal and IRI model mice to identify relevant transcription factors. Western blotting, qRT-PCR, immunohistochemical staining, and flow cytometry were performed in IRI models to indicate the effect of FOXO1 on the polarization of Th17/Treg cells. Then, transwell assay of HCC cell migration and invasion, clone formation, wound healing assay, and Th17 cells adoptively transfer was utilized to assess the function of Th17 cells in IRI-induced HCC recurrence in vitro and in vivo.
resultsOwning to the application of RNA sequencing, FOXO1 was screened and assumed to perform a significant function in hepatic IRI. The IRI model demonstrated that up-regulation of FOXO1 alleviated IR stress by attenuating inflammatory stress, maintaining microenvironment homeostasis, and reducing the polarization of Th17 cells. Mechanistically, Th17 cells accelerated IRI-induced HCC recurrence by shaping the hepatic pre-metastasis microenvironment, activating the EMT program, promoting cancer stemness and angiogenesis, while the upregulation of FOXO1 can stabilize the liver microenvironment homeostasis and alleviate the negative effects of Th17 cells. Moreover, the adoptive transfer of Th17 cells in vivo revealed its inducing function in IRI-induced HCC recurrence.
conclusionsThese results indicated that FOXO1-Th17/Treg axis exerts a crucial role in IRI-mediated immunologic derangement and HCC recurrence, which could be a promising target for reducing the HCC recurrence after hepatectomy. Liver IRI affects the balance of Th17/Treg cells by inhibiting the expression of FOXO1, and the increase of Th17 cells has the ability to induce HCC recurrence through EMT program, cancer stemness pathway, the formation of premetastatic microenvironment and angiogenesis.
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