UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5)

Mechanistic studies revealed that CIRP facilitated the interaction between the E3 ubiquitin ligase UBR5 and ACSL4, leading to increased ubiquitination and subsequent proteasomal degradation of ACSL4. In summary, our findings indicate that CIRP advances glioma progression via inhibiting ferroptosis through the promotion of UBR5-mediated ACSL4 degradation.

Bone metastasis is an adverse prognostic factor for progression-free survival in lung adenocarcinoma patients treated with third-generation EGFR-TKIs. Bone metastasis lesions exhibit a distinct immunosuppressive tumor microenvironment in EGFR-mutant advanced lung adenocarcinoma, in which upregulation of immune regulatory genes in cancer cells and dysfunction of immune cells may constitute a potential mechanism underlying resistance to third-generation EGFR-TKIs.

This process is mediated by circ-UBR5 binding to HNRNPR. High expression of circ-UBR5 and HNRNPR in tumor tissues correlates with poor prognosis in patients with LUAD, indicating their potential as novel prognostic biomarkers and therapeutic targets for LUAD.

The present study underscores the pivotal function of ACAT2 in CC progression and delineates its potential as a therapeutic latent strategy. This approach involves the strategic obstruction of the metabolic pathway associated with ACAT2.

Collectively, our findings demonstrate that NaF activates the PINK1/Parkin-mediated mitophagy pathway; however, incomplete autophagic degradation leads to mitochondrial dysfunction and neuronal apoptosis, contributing to developmental neurotoxicity. Importantly, melatonin mitigates these adverse effects, suggesting its potential as a therapeutic agent for preventing fluoride-induced neurodevelopmental impairment through modulation of the PINK1/Parkin signaling axis.

This study unveils a previously unrecognized oncogenic mechanism wherein USP18 promotes malignant progression of nasopharyngeal carcinoma via UBR5-dependent suppression of the p53 signaling pathway. These findings highlight USP18 as a promising candidate biomarker and potential therapeutic target in NPC.

The results show that downregulating LINC01106 significantly inhibited proliferation, migration, and invasion capabilities of GC cells, while inducing cell cycle arrest at the G2/M phase; mechanistically, LINC01106 regulate the expression of Denticleless E3 Ubiquitin Protein Ligase Homolog (DTL) by sponging miR-361-3p; moreover, TME analysis reveale that high DTL expression was associated with reduced immune cell infiltration, decreased stromal cell proportion, and elevate tumor cell purity in GC tissues, with significant correlations also observed with immune checkpoint molecule expression. This study suggests that the LINC01106/miR-361-3p/DTL network accelerates GC progression by promoting cell cycle progression and remodeling the TME, providing a novel potential molecular target for targeted therapy of gastric cancer.

Notably, combining circUBR5-targeting antisense oligonucleotides with cisplatin synergistically inhibited tumor growth and reversed chemoresistance in vivo. Thus, circUBR5 promotes GSRCC progression through dual pathways coordinating estrogen signaling and cholesterol metabolism, and its exosomal dissemination facilitates chemoresistance induction within the tumor microenvironment, highlighting its potential as a prognostic biomarker and therapeutic target.

Additionally, attenuated EC angiogenesis was achieved solely by silencing SLC25A6. Our findings highlight that XPNPEP2 regulates angiogenesis via modulation of mitochondrial function, which may represent a new strategy for the treatment of angiogenesis-related diseases.

As a feedback mechanism, upon estrogen (E2) stimulation, E2-bound ERα activates non-genomic MAPK signaling to trigger SIRT7 degradation via another E3 ligase UBR5, which ensures the proper receptor signaling activation. Given the central role of ERα in aging and hormone-related cancers, our findings highlight SIRT7 as a key regulator linking age-associated disorders and hormone-driven tumorigenesis.

These findings suggest that PELI3 could serve as a valuable prognostic marker in NSCLC and may represent a promising target to improve tumor sensitivity to radiotherapy.

Furthermore, HERC1 overexpression enhanced the inhibition of gemcitabine on tumor growth by suppressing autophagy in vivo. In conclusion, HERC1 inhibited autophagy by inactivating PIK3CB-mediated PI3K/AKT signaling via promoting KAT2A degradation, thereby enhancing the gemcitabine sensitivity in lung cancer.