TOP2A (DNA topoisomerase 2-alpha)

Our study identifies a four-gene cell cycle signature associated with poor LUAD prognosis and demonstrates that astragalin induces apoptosis in LUAD cells. These genes are involved in a PANoptosis-related network, suggesting a potential mechanistic link requiring further validation.

This comprehensive single-cell transcriptomic analysis successfully characterized the cellular heterogeneity of glioma, identifying distinct cell populations and molecular signatures. PLP1, FTH1, and GM42418 were validated as potential molecular biomarkers, providing novel insights into glioma pathogenesis and potential therapeutic targets.

Functional experiments showed that TOP2A knockdown inhibited proliferation, migration, and invasion of NB cells. We established an eight-gene PANoptosis-related prognostic index for neuroblastoma and highlighted four hub genes (KIF18A, EXO1, TOP2A, and TACC3) closely associated with NB risk and prognosis.

PLD demonstrated modest efficacy in metastatic BC lacking HER2 overexpression, with comparable outcomes in HER2-low and HER2-negative subgroups. These findings suggest that HER2-low status does not predict anthracycline benefit and support the view that HER2-low is unlikely to represent a distinct therapeutic subtype. Further research is needed to refine treatment selection in this heterogeneous population.

This integrated computational study prioritized a five-gene framework potentially linking OTA-related predicted targets with CRC-associated metabolic and immune-related molecular alterations. These findings are supported by immune contexture inference, external protein-level reference data, computational structural analyses, and single-cell-based in silico perturbation results, providing a hypothesis-generating framework for subsequent experimental investigations into the potential toxicological relevance of OTA in CRC.

The resulting splice site gene-edited clone, designated MX2/SS-Edit, expressed reduced TOP2α/160 mRNA/protein, increased TOP2α/170 mRNA/protein, and exhibited partial restoration of sensitivity to mitoxantrone, etoposide, and amsacrine. SIGNIFICANCE STATEMENT: Results presented here validated drug resistance in the HL-60/MX2 leukemia cell line driven by intronic polyadenylation (IPA) within intron 33 of the DNA topoisomerase IIα (TOP2α) gene, which produced a truncated and predominantly cytoplasmic TOP2α protein isoform (TOP2α/160). Using CRISPR/Cas9/homology-directed repair gene editing, the weak exon 33/intron 33 5' splice site was enhanced to suppress IPA, which restored expression of full-length protein (TOP2α/170) and led to a gain-of-function in drug sensitivity, offering a potential strategy to overcome drug resistance.

Redocking of co-crystallized ligands yielded RMSD values below 2.0 Å, supporting protocol reliability. Overall, these findings suggest preliminary dark-condition in vitro activity of SiPc (Tan et al., 2020 (4)) and SubPc (Weller et al., 2021 (5)) against U-87 MG cells, while the docking results offer hypothesis-generating molecular insight into possible target interactions that may support future mechanistic and optimization studies.

This integrative study provides a comprehensive single‑cell and spatial atlas of baicalein‑responsive genes in NSCLC, identifies a robust diagnostic signature, and offers mechanistic insights for developing baicalein as a potential therapeutic agent.

Topoisomerase II (TOP2) poisons, such as etoposide, are potent antineoplastic drugs that also cause significant secondary toxicity to postmitotic cells...Intriguingly, HSF1 preferentially stimulates TOP2B over TOP2A, and knockdown or inhibition of HSF1 reduces the levels of catalytically engaged TOP2B but not TOP2A. Moreover, HSF1 inhibitors suppress the cytotoxicity of TOP2 poisons toward postmitotic cells without compromising their ability to kill cancer cells, revealing a strategy for minimizing the side-effects of TOP2 poison-based chemotherapy.

Variant T-allele carriers (CT or TT) exhibited approximately 30% lower DOX EC50 than CC homozygotes in both the training and the test sets. Comprehensive analysis of common diversity in genetic loci coding for human topoisomerases identified rs113270903 in TOP3A as a new promising determinant of DOX sensitivity.

This study presents a lactylation-related risk score model with significant potential for improving the management of PDAC patients. The identification of the lactate-TOP2A-H3K18la-NQO1 axis enhances the understanding of lactylation mechanisms in PDAC, thereby providing a foundation for targeted therapeutic approaches.

While ICRF-193 suppressed tumor growth, Top2βf/f deficiency (with a compensatory TOP2α upregulation) enhanced tumor development, indicating potential roles for TOP2 isozymes in tumor formation and progression. Collectively, these findings identify the cooperative action of TOP2 and NOS2 in driving DSBs, highlighting a potential therapeutic target in inflammation-associated CRC.