NEDD4 (NEDD4 E3 Ubiquitin Protein Ligase)

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.

Our data further demonstrated that pharmacological or genetic inhibition of c-Myc effectively reversed the resistance phenotype mediated by HDAC5 loss, suggesting a therapeutic strategy centered on "KRAS-MYC dual-node blockade." Furthermore, the expression levels of HDAC5 and the acetylation status of c-Myc may serve as potential biomarkers for predicting the therapeutic response to MRTX1133. These findings provide insights into overcoming resistance to KRASG12D inhibitors and offer potential biomarkers and combinatorial therapeutic strategies for precision treatment of PDAC.

N4BP2 promoted genome rearrangements (including chromothripsis), formation of extrachromosomal DNA (ecDNA) in drug-induced gene amplification, tumorigenesis, and tumor cell proliferation in an induced model of human high-grade glioma. Analysis of more than 10,000 human cancer genomes revealed elevated N4BP2 expression to be predictive of chromothripsis and copy number amplifications, including ecDNA.

In conclusion, this study further identifies NDFIP1 as a novel target of PF-429242, partially responsible for its induction of autophagy in HCC cells. These findings offer a promising therapeutic avenue for treating HCC.

Increased matrix stiffness significantly promoted glycolysis in HCC cells via upregulating PFKFB3 expression. High stiffness stimulation suppressed PFKFB3 ubiquitination by downregulating E3 ubiquitin ligase NEDD4 expression. PFKFB3 participated in DNA damage repair by translocating into nuclear and interacting with Ku70, which strengthened by matrix stiffness.

miR-155-5p emerges as a promising diagnostic marker and therapeutic candidate, suggesting the feasibility of miRNA-based interventions in BC treatment. This study highlights the pivotal role of integrative omics technologies in uncovering cancer-related regulatory networks.

Furthermore, a small-molecule inhibitor of NEDD4, XMU-MP-10, exhibits significant in vivo efficacy in inhibiting TNBC tumor growth by enhancing CD8+ T cell infiltration in mouse models. Collectively, our findings suggest that the genetic depletion or pharmacological inhibition of NEDD4 enhances antitumor immune responses via the β-TrCP/YAP/ECM cascades, offering a promising therapeutic strategy for TNBC treatment.