UBE2H (Ubiquitin Conjugating Enzyme E2 H)

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.

In conclusion, E2F8 promotes EC progression by transcriptionally activating DTL and activating the MAPK pathway. These findings provide novel mechanistic insights into EC progression and suggest that the E2F8/DTL/PDCD4/MAPK axis may serve as a potential therapeutic target for EC.

This study revealed the presence of a UBE2H+ cell population within the pancreatic ductal cell niche and analyzed the inhibition of UBE2H on the immune microenvironment of pancreatic cancer through single-cell sequencing and in vivo experiments, providing important clues for the formation of "cold" tumors in pancreatic cancer and opening new directions for exploring new treatment strategies.

OPN enhances tumor proliferation and survival through mechanistic target of rapamycin and B-cell lymphoma 2 upregulation (e.g., via denticleless E3 ubiquitin protein ligase homolog in hepatocellular carcinoma) and drives metastasis via PI3K/AKT-mediated epithelial-mesenchymal transition and androgen receptor (AR) activation (e.g., via the OPN-RAN-AR axis in pancreatic cancer)...Therapies targeting the OPN-PI3K/AKT axis (e.g., PI3K inhibitors like LY294002) or combination treatments (e.g., with EGFR-TKIs) show promise for reversing drug resistance. Future research should focus on OPN isoform specificity, clinical translation, and interactions with autophagy and long non-coding RNAs to refine precision therapies. This review summarizes recent advances in understanding the molecular mechanisms, therapeutic targets, and clinical challenges of the OPN-PI3K/AKT axis in gastrointestinal tumors, providing a foundation for overcoming resistance and developing precision therapies.

Our findings suggest that UBE2H could serve as a resistance marker to oxaliplatin, as it is associated with methylation, the presence of proliferative and undifferentiated cancer cells, and immune exhaustion. The proposed analytical pipeline may also be applicable to other cancers and diseases.

(DTL) exhibits potential as a novel biomarker for distinguishing between benign and malignant adrenocortical tumors and may serve as a prognostic indicator for ACC.

The identified gene subset provides novel prognostic insights into PCa progression and survival. These findings highlight potential biomarkers and therapeutic targets within the ubiquitin-proteasome pathway, offering new avenues for personalized treatment strategies.

This study identified 10 key genes related to stemness and immune cell infiltration in HCC. These genes, primarily involved in cell cycle regulation, may serve as potential targets for developing more effective treatments to reduce HCC recurrence and improve patient outcomes.

DTL promotes the ubiquitination of SAFB-like transcription modulator (SLTM) and subsequently relieves the transcriptional repression of Notch1. These results suggested that DTL may be a potential biomarker and therapeutic target for HCC.

MiR-96-5p agomir treatment slowed the growth of transplanted HaCaT cells transformed by arsenite in a manner associated with DTL downregulation in the nude mice xenograft model. Taken together, we confirmed that miR-96-5p, as a potent regulator of DTL, suppressed arsenite-induced HaCaT cell proliferation and malignant transformation, which might provide a novel therapeutic target for the treatment of arsenic-induced skin cancer.

USP18 impairs ubiquitination and subsequent degradation of CSF1R by interrupting NEDD4 binding to CSF1R. These results reveal a previously unappreciated role of IFN-I in macrophage polarization by regulating CSF1R via USP18 and suggest targeting USP18 in myeloid-lineage cells as an effective strategy for IFN-based therapies.

To conclude, this study has shown that NUP93 has pro-tumor properties in ESCC and that HECTD1 functions as an upstream regulator of NUP93 in ESCC. These findings may contribute to the investigation of potential therapeutic targets in ESCC.