ArticleExperimental & molecular medicine2022
Oncogenic E3 ubiquitin ligase NEDD4 binds to KLF8 and regulates the microRNA-132/NRF2 axis in bladder cancer.
Article in Experimental & molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Fine-Tuning Protein Fate: Mechanisms of E1, E2, and E3 Enzymes and Deubiquitinases in Cell Signaling.International journal of molecular sciences · 2026Review
- Comprehensive analysis of the role of NEDD4 in pan-cancer and experimental verification of its role in KIRC progression.Discover oncology · 2025Article
- Article
- NEDD4 facilitates the progression of endometrial carcinoma by enhancing PAMR1 protein degradation through ubiquitination.Functional & integrative genomics · 2025Article
- BHLHE41 inhibits bladder cancer progression via regulation of PYCR1 stability and thus inactivating PI3K/AKT signaling pathway.European journal of medical research · 2024Article
- ECHDC2 inhibits the proliferation of gastric cancer cells by binding with NEDD4 to degrade MCCC2 and reduce aerobic glycolysis.Molecular medicine (Cambridge, Mass.) · 2024Article
- MicroRNAs participate in the regulation of apoptosis and oxidative stress-related gene expression in rabbits infected withFrontiers in microbiology · 2024Article
- Ubiquitin ligase NEDD4 promotes the proliferation of hepatocellular carcinoma cells through targeting PCDH17 protein for ubiquitination and degradation.The Journal of biological chemistry · 2024Article
- FAT10 mediates the sorafenib-resistance of hepatocellular carcinoma cells by stabilizing E3 ligase NEDD4 to enhance PTEN/AKT pathway-induced autophagy.American journal of cancer research · 2024Article
- Potential roles of NEDD4 and NEDD4L and their utility as therapeutic targets in high‑incidence adult male cancers (Review).Molecular and clinical oncology · 2023Review
- Review
- Review
- E3 ubiquitin ligases and deubiquitinases in bladder cancer tumorigenesis and implications for immunotherapies.Frontiers in immunology · 2023Review
- The role of E3 ubiquitin ligases and deubiquitinases in bladder cancer development and immunotherapy.Frontiers in immunology · 2023Review
- Arbutin-modified microspheres prevent osteoarthritis progression by mobilizing local anti-inflammatory and antioxidant responses.Materials today. Bio · 2022Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The neuronally expressed developmentally downregulated 4 (NEDD4) gene encodes a ubiquitin ligase that targets the epithelial sodium channel for degradation and has been implicated in tumor growth in various cancers. Hence, in this study, we intended to characterize the functional relevance of the NEDD4-mediated Kruppel-like factor 8/microRNA-132/nuclear factor E2-related factor 2 (KLF8/miR-132/NRF2) axis in the development of bladder cancer. NEDD4 and KLF8 were overexpressed in bladder cancer tissues and were associated with poorer patient survival rates. In bladder cancer cells, NEDD4 intensified the stability and transcriptional activity of KLF8 through ubiquitination to augment cell viability and migratory ability. Our investigations revealed that NEDD4 promotes the binding of KLF8 to the miR-132 promoter region and inhibits the expression of miR-132. KLF8 inhibited the expression of miR-132 to augment the viability and migratory ability of bladder cancer cells. Furthermore, miR-132 downregulated the expression of NRF2 to restrict the viability and migratory ability of bladder cancer cells. In addition, in vivo findings verified that NEDD4 regulates the KLF8/miR-132/NRF2 axis by accelerating tumor growth and lung metastasis. In conclusion, this study highlights NEDD4 as a potential therapeutic target against tumor recurrence and metastasis in bladder cancer.
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