NEDD4 (NEDD4 E3 Ubiquitin Protein Ligase)

Importantly, early interventions targeting this axis - including Bifidobacterium pseudolongum supplementation, overexpressing IGSF9, and C1q neutralization - effectively prevented MAFLD-HCC progression in preclinical models. These findings provide preliminary evidence that the E. faecalis/IGSF9/C1q axis could be involved in MAFLD-HCC, with IGSF9 may serve as both a prognostic biomarker and therapeutic target, which worth further exploration in future studies.

Specifically, hypoxia-induced alternative splicing of SRSF6 mRNA produced a long transcript containing a poison cassette exon, which led to nonsense-mediated mRNA decay. In conclusion, this study identifies a tumor suppressive tRF that enhances ferroptosis sensitivity in HCC and illustrates the potential of tRFs in cancer treatment.

NEDD4 overexpression suppressed LUAD growth both in vitro and in vivo, effects that were reversed by ZBTB7B restoration. Collectively, this work reveals a novel NEDD4/ZBTB7B/ ADPGK axis that integrates transcriptional and post-translational regulation of glycolysis, offering potential therapeutic targets for metabolic intervention in LUAD.

TN-induced PTGS2 downregulation leads to the inhibition of the JAK/STAT3/c-Myc signaling axis, resulting in suppression of tumor proliferation and the induction of autophagic cell death. In conclusion, our findings highlight TN as a promising candidate for TNBC and EOC treatment, acting through a novel mechanism involving targeted degradation of PTGS2 protein.

Mechanistically, XMU-MP-9 acts as a bifunctional compound to bind the C2 domain of NEDD4-1 and an allosteric site of K-RAS to enhance NEDD4-1 and K-RAS interaction, and to induce a conformational change of NEDD4-1/K-RAS complex to allow NEDD4-1 targeting K128 of K-RAS for ubiquitination. Hence, our study presents an effective way to degrade K-RAS mutants to prevent tumor development.

Recurrent insertions were located near cancer-associated genes, including RB1, NEDD4, FTO, LAMA2, NOD1, and KCNB2, implicating LINE-1 activity in cis-regulatory remodeling of oncogenic pathways. Together, these findings indicate that LINE-1 transcript heterogeneity in NSCLC is shaped by host genomic architecture and conserved functional hotspots, providing new insights into the mechanisms of genetic and epigenetic dysregulation associated with LINE-1 retroelements.

Based on molecular docking and molecular dynamics results, NEDD4L is believed to be a 18β-GRA biomarker, while sodium channel protein type 5 subunit alpha (SCN5A) and early growth response protein 1 (EGR1) are the potential upstream and downstream regulatory proteins, respectively. These findings provide a theoretical basis for future experimental verification.

Additionally, exosomal LCN2 could be a potential biomarker for HCC diagnosis and prognosis. However, further pre-clinical and clinical studies are needed to validate these findings.

Furthermore, although we were unable to confirm the binding of TMEM207 to NEDD4, we confirmed the binding of TMEM207 to the Yes1-associated transcription factor (YAP) by immunoprecipitation, and a decrease in the nuclear localization of YAP was observed by immunohistochemical staining. Our findings indicate that abnormal expression of TMEM207 is involved in the decline of skin regeneration capacity through YAP, leading to the aggravation of Allergic contact dermatitis.

Furthermore, in TMX1-overexpressing HuH-7 cells, FABP5 knockdown negated the effects of TMX1 overexpression, suggesting that FABP5 mediates TMX1's regulation of HCC cell proliferation. Consequently, this study elucidates the mechanisms by which TMX1 contributes to HCC development, suggesting that TMX1 may serve as a potential biomarker and therapeutic target in the context of HCC.

In vivo study demonstrates that the siRNA@NPs-hydrogel system significantly reduced the weight of the xenograft KD tissue, substantially lowered the expression of NEDD4, Col1a1, and Col3a1, and significantly induced the apoptosis level. Overall, our findings suggest that local delivery of si-NEDD4 via a nanoparticle-hydrogel sustained-release system may represent a promising approach for the treatment of KD.

p53 critically influences the development and progression of musculoskeletal diseases (osteoporosis, osteoarthritis, rheumatoid arthritis, low back pain, gout, and scoliosis) through diverse mechanisms: Disrupting bone formation/resorption balance (via the p53-Nedd4-Runx2 axis in osteoporosis). Promoting chondrocyte apoptosis (via the miR-34a-SIRT1-p53 pathway in osteoarthritis). Modulating inflammatory mediators (TNF-α, IL-6 in rheumatoid arthritis). Regulating oxidative stress responses (p53-SLC2A9 axis in gout). p53 exhibits dual roles (pro-apoptotic vs. anti-inflammatory), necessitating precise targeting strategies. Promising therapeutic interventions include p53-focused gene editing (CRISPR/Cas9), small-molecule inhibitors (PFT-α), and natural products (naringin). However, further clinical validation is essential. Future research requires multidisciplinary approaches to deepen understanding of p53 mechanisms and advance clinical applications in musculoskeletal disorders.