ArticleJournal of advanced research2025
E3 ubiquitin ligase RNF128 attenuates colitis and colorectal tumorigenesis by triggering the degradation of IL-6 receptors.
Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- TNF-α-responsive YAP1 promotes CCL20 expression in colorectal inflammation and cancer.Scientific reports · 2026Article
- Eubacterium rectale Mitigates Inflammatory Bowel Disease via Modulation of Glutamine Metabolism Through the GLS2 and NF-κB Pathway.NPJ science of food · 2026Article
- Ubiquitin-Modifying Enzymes as Cell-Fate Regulators in Intestinal Inflammation.International journal of biological sciences · 2026Review
- Cardiomyocyte-Specific RNF128 Attenuates Pathological Cardiac Hypertrophy Progression by Stabilizing SERCA2a through Lys63-Linked Polyubiquitination.Theranostics · 2026Article
- Regulatory roles of E3 ubiquitin ligase RNF128 in inflammatory diseases and tumors.Journal of Cancer · 2026Review
- YY1 induced USP13 transcriptional activation drives the malignant progression of hepatocellular carcinoma by deubiquitinating WWP1.Cellular & molecular biology letters · 2025Article
- RNF128 deficiency in macrophages promotes colonic inflammation by suppressing the autophagic degradation of S100A8.Cell death & disease · 2025Article
- E3 ligase RNF128 restricts A. alternata-induced ILC2 activation and type 2 immune response in the murine lung.Scientific reports · 2025Article
- Ubiquitination Enzymes in Cancer, Cancer Immune Evasion, and Potential Therapeutic Opportunities.Cells · 2025Review
- Gut Microbiota and Metabolites Mediate Health Benefits of Oat and Oat Bran Consumption in IBD Mice.Nutrients · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionIntestinal immune dysregulation is strongly linked to the occurrence and formation of tumors. RING finger protein 128 (RNF128) has been identified to play distinct immunoregulatory functions in innate and adaptive systems. However, the physiological roles of RNF128 in intestinal inflammatory conditions such as colitis and colorectal cancer (CRC) remain controversial.
objectivesTo elucidate the function and mechanism of RNF128 in colitis and CRC.
methodsAnimal models of dextran sodium sulfate (DSS)-induced colitis and azoxymethane (AOM)/DSS-induced CRC were established in WT and Rnf128-deficient mice and evaluated by histopathology. Co-immunoprecipitation and ubiquitination analyses were employed to investigate the role of RNF128 in IL-6-STAT3 signaling.
resultsRNF128 was significantly downregulated in clinical CRC tissues compared with paired peritumoral tissues. Rnf128-deficient mice were hypersusceptible to both colitis induced by DSS and CRC induced by AOM/DSS or APC mutation. Loss of RNF128 promoted the proliferation of CRC cells and STAT3 activation during the early transformative stage of carcinogenesis in vivo and in vitro when stimulated by IL-6. Mechanistically, RNF128 interacted with the IL-6 receptor α subunit (IL-6Rα) and membrane glycoprotein gp130 and mediated their lysosomal degradation in ligase activity-dependent manner. Through a series of point mutations in the IL-6 receptor, we identified that RNF128 promoted K48-linked polyubiquitination of IL-6Rα at K398/K401 and gp130 at K718/K816/K866. Additionally, blocking STAT3 activation effectively eradicated the inflammatory damage of Rnf128-deficient mice during the transformative stage of carcinogenesis.
conclusionRNF128 attenuates colitis and colorectal tumorigenesis by inhibiting IL-6-STAT3 signaling, which sheds novel insights into the modulation of IL-6 receptors and the inflammation-to-cancer transition.
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