Background: Osteosarcoma (OS) is a tumour with a high malignancy level and a poor prognosis. First-line chemotherapy for OS has not been improved for many decades. Bromodomain and extraterminal domain (BET) and histone deacetylases (HDACs) regulate histone acetylation in tandem, and BET and HDACs have emerged as potential cancer therapeutic targets. Methods: Cell proliferation, migration, invasion, colony formation, and sphere-forming assays were performed with the two inhibitors alone or in combination to evaluate their suppressive effect on the malignant properties of OS cells. Apoptosis and the cell cycle profile were measured by flow cytometry. The synergistic inhibitory effect of OTX015/WT-161 on tumours was also examined in a nude mouse xenograft model. Results: The combined therapy of OTX015/WT-161 synergistically inhibited growth, migration, and invasion and induced apoptosis, resulting in G1/S arrest of OS cells. Additionally, OTX015/WT-161 inhibited the self-renewal ability of OS stem cells (OSCs) in a synergistic manner. Further mechanistic exploration revealed that the synergistic downregulation of β-catenin by OTX015-mediated suppression of FZD2 and WT-161-mediated upregulation of PTEN may be critical for the synergistic effect. Finally, the results of an in vivo assay showed that tumour xenografts were significantly decreased after treatment with the OTX015/WT-161 combination compared with OTX015 or WT-161 alone. Conclusions: Our findings in this study demonstrated that OTX015 and WT-161 had synergistic anticancer efficacy against OS, and their combination might be a promising therapeutic strategy for OS.

Aim: This study aimed to explore the genetic and epigenetic similarities between chronic obstructive pulmonary disease (COPD) and lung adenocarcinoma (LUAD). Materials & methods: We mainly used Wei...

Ferroptosis, a form of regulated cell death, plays a pivotal role in the development and treatment of cancer because of its impact on tumor cell proliferation, differentiation, and resistance to chemotherapy. NT5DC2, a gene associated with ferroptosis, has been identified as a key facilitator of cellular proliferation and metastasis in several cancers. In this study, we found that NT5DC2 is highly expressed in bladder cancer tissues compared with normal tissues and that its expression is correlated with the poor prognosis of bladder cancer patients. Functionally, we demonstrated that NT5DC2 suppresses ferroptosis in bladder cancer cells and promotes malignant tumor progression. Mechanistically, NT5DC2 interacts with ACSL3 and hampers its ubiquitination, thereby improving the stability of ACSL3, a crucial ferroptosis suppressing protein induced by oleic acid in lymph nodes. In addition, rescue assay results indicated that ACSL3 mediated the roles of NT5DC2 in suppressing ferroptosis of bladder cancer cells. Furthermore, we found that the upregulation of ACSL3 by oleic acid treatment was mediated by NT5DC2 as manifested by the observation that silencing of NT5DC2 abrogates this regulatory effect of oleic acid treatment. Collectively, our findings suggest that NT5DC2/ACSL3 plays a critical role in bladder cancer progression and ferroptosis regulation, suggesting that NT5DC2/ACSL3 is a potential therapeutic target for bladder cancer treatment.

Background: Lung squamous cell carcinoma (LUSC) remains an aggressive malignancy with limited therapeutic options and poor prognosis. Recent studies have identified disulfidptosis as a novel form of metabolic stress-induced cell death, but its clinical implications in LUSC remain unexplored. This study investigates the prognostic value of disulfidptosis-related genes (DRGs) in LUSC. Methods: We analyzed transcriptomic data from TCGA-LUSC cohort and identified DRGs through intersection with established disulfidptosis-related gene sets. A protein-protein interaction (PPI) network was constructed, and univariate Cox regression was performed to select prognostic genes. A risk score model was developed using multivariate Cox regression. The model’s performance was evaluated using ROC curve and Kaplan-Meier analyses. Functional enrichment and immune microenvironment analyses were conducted to explore potential mechanisms. Results: We identified 9 prognostic DRGs (FHOD1, ORC5, TRIR, ALKBH1, EPS8L2, MBLAC1, MYADM, HTRA2, and SRI) that significantly correlated with patient survival. The risk score model effectively stratified patients into high- and low-risk groups ( P < 0.001), with C-index values of 0.78 at 1 year and 0.75 at 3 years. High-risk patients showed enriched cytokine-cytokine receptor interactions and immunosuppressive microenvironments, while low-risk patients exhibited activated metabolic pathways. Experimental validation confirmed ORC5’s oncogenic role in promoting proliferation and invasion. Conclusion: We established a novel 9-gene prognostic signature based on disulfidptosis-related genes that effectively predicts LUSC outcomes. These findings highlight the clinical relevance of disulfidptosis in LUSC and provide potential biomarkers for risk stratification and therapeutic targeting.

Background: Osteosarcoma (OS) is a tumor with a high malignancy level and a poor prognosis. First-line chemotherapy for OS has not been improved for many decades. Bromodomain and extra terminal domain (BET) and histone deacetylase (HDACs) regulate histone acetylation in tandem, and BET and HDACs have emerged as potential cancer therapeutic targets. Methods: Cell proliferation, migration, invasion, colony formation, and sphere-forming assay were performed with the two inhibitors alone or in combination to evaluate their suppressing effect on malignant properties of OS cells. The apoptosis and cells-cycle profile were measured by flow cytometry. The synergistic inhibitory effect of OTX015/WT-161 on tumor was also examined in a nude mouse xenograft model. Results: The combined therapy of OTX015/WT-161 synergistically inhibited the growth, migration, and invasion and induced apoptosis, resulted in the G1/S arrest of OS cells. Additionally, OTX015/WT-161 inhibits the self-renewal ability of OS stem cells (OSCs) in a synergistic manner. Further mechanistic exploration uncovered that the synergistic downregulation of β-catenin by OTX015-mediated suppression of FZD2 and WT-161-mediated upregulation of PTEN may be responsible for the synergistic effect. Finally, the result of an in vivo assay showed that tumor xenografts were significantly decreased after treatment with OTX015/WT-161 combination compared with OTX015 or WT-161 alone. Conclusion: Our findings in this study demonstrated that OTX015 and WT-161 had a synergistic anti-cancer efficacy against OS, and their combination might be a promising therapeutic strategy for OS.