OXCT1 (3-Oxoacid CoA-Transferase 1)

In breast cancer models, elevated RAD51 succinylation correlates with reduced HR capacity and increased sensitivity to the PARP inhibitor olaparib, whereas diminished succinylation confers resistance. Moreover, a cell-penetrating peptide that disrupts the RAD51-HDAC11 interaction increases RAD51 succinylation and synergizes with chemotherapy. Collectively, our findings uncover a metabolic-epigenetic mechanism linking protein succinylation to HR and genomic stability and identify RAD51 succinylation as a predictive biomarker and therapeutic target in cancer.

This review systematically summarizes the molecular structure, biological functions, and regulatory mechanisms of OXCT1, highlighting its multifaceted roles in tumorigenesis and progression. Furthermore, we discuss its potential as a diagnostic biomarker, prognostic indicator, and therapeutic target, providing novel insights for developing OXCT1-based anticancer strategies.

Our research suggested the OXCT1/Wnt signaling axis pathway as a critical regulator of CRLM. And these findings offered valuable insights, and potential therapeutic targets for CRLM.

Our findings further suggest that these hub genes may serve dual purposes: as indicators of early viral infection, including COVID-19 and related viral illnesses, and as potential predictors of cardiovascular disease (CVD) onset following COVID-19 infection. This work strongly urges health policymakers to implement screening for COVID-19 complications, especially CVDs, in the general public.

In vitro and in vivo validation demonstrated that iOXCT1 suppresses HCC growth via OXCT1 inhibition. Collectively, our results establish OXCT1 as a promising therapeutic target and identify iOXCT1 as a novel dual-activity inhibitor, providing a foundation for developing OXCT1-targeted therapies against HCC.

In conclusion, OXCT1 interference reverses the KMT5A-induced enhancement of TNBC cell viability, proliferation, and PD-L1 expression. KMT5A promotes OXCT1 expression through histone methylation, and OXCT1 increases PGK1 protein stability through succinylation modification, thereby promoting aerobic glycolysis and immune escape in TNBC.

Therefore, investigating the molecular mechanisms involved in the pathogenesis of gastrointestinal malignancies is essential for clinical treatment. This article summarizes the biological roles and molecular mechanism of circRNAs in EMT of gastrointestinal malignancies, providing a theoretical basis for applying EMT-related circRNAs in targeted therapy.

Immunohistochemical analysis further confirmed that high expression of these six genes was significantly associated with poor prognosis in NPC patients, a trend corroborated by data from the TCGA head and neck cancer cohort. This study highlights the pivotal roles of key molecular players in therapeutic response in NPC, providing compelling evidence for their potential application as prognostic biomarkers and therapeutic targets, thereby contributing to precision oncology strategies aimed at improving patient outcomes.

Notably, treatment with acetohydroxamic acid, an OXCT1 inhibitor used clinically for urinary infection, inhibits liver tumor growth in mice and significantly enhances lenvatinib therapy. Our findings highlight the role of SUCLA2-coupled regulation of OXCT1 succinylation in ketolysis and unveil an unprecedented strategy for treating HCC by interrupting ketolysis.

Building on previous research that identified metastatic-niche-specific metabolic vulnerabilities, we investigated how a ketogenic diet enhances estrogen receptor (ER)-positive liver metastatic breast cancer's response to Fulvestrant (Fulv) treatment...We also explored interactions between glucose, palmitic acid, and β-hydroxybutyric acid. These findings establish the molecular basis and clinical potential of a ketogenic diet to enhance Fulv efficacy in patients with ER+ liver metastatic breast cancer, potentially improving survival outcomes and quality of life in this population.

The KO of OXCT1 restored OVOL1 transcriptional repressive activity by its nuclear translocation. Orthotopic mouse models of BCa supported OXCT1 as a mediator of gemcitabine sensitivity through ketone metabolism and regulating cancer stem cell differentiation.

Elasticnet model tuning on individual marker expression revealed top tumor predictive markers, including FKBP10, ATP1A2, NT5DC2, UGT3A2, PYCR1, CKB, GPX7, DNMT3B, GSTP1, and OXCT1. These findings indicate that an activated metabolic transcriptional program, potentially influencing epigenetic functions, is observed in hepatoblastoma tumors and confirmed at the single-cell level.