PSMA2 (Proteasome 20S Subunit Alpha 2)

Androgen deprivation therapy (ADT) and next-generation AR blockade (e.g., enzalutamide) are initially effective, but virtually all patients develop castration-resistant prostate cancer (CRPC), which frequently transitions to treatment-emergent neuroendocrine PCa (tNEPC) following AR suppression...Thus, we uncover a single stress-induced node (PSMA2) that both maintains AR-dependent survival under ADT and fuels the neuroendocrine transition. PSMA2 marks an AR-hypersensitized transitional state and is itself a therapeutically actionable driver of tNEPC evolution, revealing an opportunity for rational interception of the lethal ADT-CRPC-tNEPC trajectory.

These findings demonstrate, for the first time, that METTL14 modulates the expression of genes related to TNF, IFN, IL, and MHC class I in NPC, proposing a novel role for METTL14 in linking inflammation with cancer, a function that has not been fully elucidated.

Salivary exosomes in the UC patients may have the function of promoting inflammation. Analysis of protein levels in the saliva of the UC patients and healthy controls revealed significant differences in the expression levels of 15 co-expressed proteins between the two groups. Among them, C3, PSMA2, PSMB6 and PSMA1 were found to be mainly related to immune and inflammatory reactions in the UC group. These findings suggest that proteins with high specific expression in salivary exosomes of the UC patients have the potential to be used as a disease marker for UC diagnosis and may contribute to the pathogenesis of UC.

This study revealed the critical role of B cells in cALL, and the prognostic model showed a high prediction accuracy, providing a potential target for individualized treatment of cALL.

Molecular docking studies confirmed strong binding affinity of verteporfin (ITGA4 inhibitor, docking score=-16.0 kcal/mol) and ebselen (MPO inhibitor) to their respective targets, suggesting potential therapeutic strategies to overcome chemotherapy resistance. This study establishes a robust 13-gene exosome-based prognostic signature for AML risk stratification and identifies novel immunomodulatory mechanisms mediated by exosome-driven Treg polarization.

Analysis of gene expression by qRT-PCR and differential gene expression revealed that GADD45g genes can be effective genes in the proliferation of oncolytic HSV-1 virus. The transcriptome changes in tumor cells infected by oHSV-1 may be utilized to predict oncolytic efficacy and provide rational strategies for designing next-generation oncolytic viruses.

Notably, mitophagy inducer exhibit antitumor effects in PSMA2-overexpressing OSCC xenograft mouse model. Collectively, our results provide a mechanistic understanding of the atypical function of PSMA2 in promoting OSCC recurrence.

A different IL-1 pathway gene expression was observed in the synovial tissues of early treatment-naïve RA/T2D patients, linked to decreased expression of the ubiquitin-proteasome system. These findings may provide a mechanistic explanation of the observed clinical benefits of IL-1 inhibition in patients with RA and concomitant T2D.

The growth inhibitory effect of these final shortlisted compounds was examined on a panel of GBM cell lines and compared with temozolomide through the drug sensitivity EC50 values and AUC from the PRISM Repurposing Secondary Screen, and the IC50 values were obtained from GDSC portal...Our results show GSK-2126458/omipalisib, linifanib, drospirenone, eltrombopag, nilotinib, and PD198306 as candidate drugs which can be further evaluated for their anti-tumor potential against GBM. Through this work, we identified repurposed candidate therapeutics against GBM utilizing a GSC inclusive targeting approach, which demonstrated high in vitro efficacy and can prospectively evade drug resistance. These drugs have the potential to be developed as individual or combination therapy to improve GBM outcomes.

Our study provides evidence supporting the role of PSMA2 as a regulatory factor in EMT and suggests its potential as a prognostic biomarker for glioma progression.

The seven-gene signature holds promise as a valuable tool for decision-making and prognosis prediction in patients with ovarian cancer.

UCHL3 overexpression contributes to aggressive progression, poor survival, and chemoresistance in OC. Therefore, UCHL3 may be a candidate prognostic biomarker and potential target for controlling progression and platinum resistance in OC.