PSMC2 (Proteasome 26S Subunit, ATPase 2)

This study established a robust six-gene prognostic model related to SUN modifications and anti-PD-1 therapy in GBM. The model demonstrates strong predictive ability and correlates with clinically relevant parameters, highlighting its potential utility for survival prediction and guiding therapeutic management decisions in GBM patients.

Besides, we used Lithium chloride to induce GSK3β phosphorylation which reversed the effects of PSMC2 knockdown, further validating this pathway. These findings demonstrate that PSMC2 drives GBM progression by regulating the AKT/GSK3β/β-catenin axis, positioning it as a promising biomarker and therapeutic target for GBM.

Finally, we validated the oncogenic role of PSMC2, a key gene in the proteasome complex, demonstrating its role in promoting GBM progression through cell proliferation, invasion, and epithelial-mesenchymal transition (EMT). Our findings provide novel insights into GBM heterogeneity, prognosis, and therapeutic strategies, suggesting PSMC2 as a potential therapeutic target.

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.

Besides, temozolomide resistance was associated with elevated proteasome activity that suppressed ER stress, which was restored upon inhibition of the proteasome with MG132. This boosted autophagosome nucleation, increased pro-death autophagy, and restored apoptosis in temozolomide-resistant glioblastoma cells. Finally, targeting PSMC2 provided a unique method for interrupting autophagy-mediated ER stress maintenance and temozolomide resistance in glioblastoma.

The analysis of the relative abundance of ten proteins with high confidence scores identified three DEPs: ADIPOQ, HEY2, and FUT10 as potential predictive biomarkers for treatment response. This study highlighted the identification of three potential predictive biomarkers-ADIPOQ, HEY2, and FUT10-through serum proteomic profiling in HNC patients undergoing RT, emphasizing their significance in predicting treatment response.

Importantly, the data indicated that the suppression of Hsa_circ_0007718 led to a marked decrease in the proliferation rates, migratory potential, and invasive capabilities of CRC cells. Furthermore, the study confirmed that Hsa_circ_0007718 acts as a downstream target of miR-1299, exerting its regulatory effects by inhibiting miR-1299 and thereby promoting the expression of PSMC2.

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.

PSMC2 was upregulated in glioma and promoted cancer progression by modulating the tumor immune microenvironment, cancer cell biological behavior, immune cell homeostasis, and the PI3K/AKT/mTOR pathway, providing a new option to treat glioma.

Four AA MAGs were prognostic of survival in OS patients. This MAG-based signature has the potential to offer valuable insights into the development of treatments for OS.

The classifier demonstrates remarkable performance in predicting intra-tumoral TLS abundance in both training and test sets, achieving areas under receiver operating characteristic curve (AUCs) of 92.9% and 90.2% respectively. In summary, the absence of intra-tumoral TLS abundance is associated with mTOR signaling activation and uncontrolled cell cycle progression in tumor cells, indicating unfavorable prognosis in HCC-LT.

Moreover, the expression levels of PSMCs are related to immune cell infiltrates and immunomodulatory factors in HCC. Our study indicates that PSMC genes are the potential target for precision immunotherapy and novel prognostic biomarkers for HCC.