Oxidative stress is a major pathogenic driver across disorders in which persistent redox imbalance promotes cellular injury, inflammation, mitochondrial dysfunction, and maladaptive survival responses. Circular RNAs (circRNAs) have emerged as post-transcriptional regulators of these processes by modulating circRNA–miRNA–mRNA networks, antioxidant gene programs, redox-sensitive signalling pathways, and ROS-generating enzymes. This review examines how circRNAs influence Nrf2, NF-κB, MAPK, PI3K/AKT, mitochondrial, and cell-death pathways in cancer, neurodegenerative, cardiovascular, and metabolic diseases. Rather than cataloguing disease-associated circRNAs, we apply a redox-centred, evidence-tiered, and context-dependent framework that distinguishes mechanistic support from associative findings and highlights why the same circRNA may exert protective or pathogenic effects across tissues and disease states. We further evaluate the diagnostic potential of circulating and tissue-specific circRNAs and the therapeutic relevance of synthetic circRNAs, antisense strategies, and CRISPR/Cas-based modulation. These approaches may enable pathway-directed biomarker development and targeted redox intervention, but their clinical value remains constrained by limited human validation, inconsistent circRNA and ROS assays, off-target effects, delivery barriers, immunogenicity, and uncertainty regarding host-gene disruption. Standardized methodologies, longitudinal cohorts, and integrated multi-omics studies are therefore required to establish causality, reproducibility, and translational readiness.
Poly(ADP-ribose) polymerase 1 (PARP1) is a key guardian of genome integrity and a major therapeutic target in cancer. Although its catalytic activation has been extensively studied, how PARP1 is restrained under physiological conditions yet rapidly mobilized following DNA damage has remained unclear. In this issue, Shu et al. (2026) identify poly(rC)-binding protein 1 (PCBP1) as an endogenous gatekeeper that restricts PARP1 access to damaged DNA. DNA double-strand breaks trigger SIRT7-dependent deacetylation of PCBP1, releasing this brake and enabling PARP1 to initiate DNA damage signaling. Beyond identifying a new regulator, this work uncovers an upstream licensing step in PARP1 activation and points to an alternative strategy for modulating PARP1 that complements conventional catalytic inhibition.
Radiotherapy (RT) is a cancer treatment cornerstone, driving tumor cell death via DNA damage while simultaneously remodeling the tumor immune microenvironment (TME). Chemokines play a central role in this remodeling. They integrate diverse signals, including radiation-induced DNA damage, type I interferon, hypoxia, and senescence-associated secretory programs to direct immune-cell trafficking. However, RT-induced chemokine networks are not uniformly immunostimulatory or immunosuppressive. CXCL9/10/11-CXCR3 signaling generally promotes Th1, CD8+ T-cell, and NK-cell recruitment, whereas CCL2/5-CCR2/5 and CXCL12-CXCR4 frequently support myeloid-cell infiltration, stromal repair, vasculogenesis, and immune escape. Other axes, particularly CXCL8-CXCR1/2, display context-dependent effects that may either recruit suppressive myeloid cells or promote NK-cell-mediated tumor control after RT. In this review, we synthesize current evidence using a time-dose-context framework, emphasizing how tumor type, radiation dose and fractionation, post-RT timing, and tissue compartment determine chemokine function. We further evaluate therapeutic strategies that combine RT with chemokine-axis blockade and immune checkpoint inhibition, highlighting clinical barriers including biomarker selection, patient stratification, sequencing, and on-target/off-tumor toxicity. A more precise understanding of RT-induced chemokine dynamics may enable rational combination regimens that preserve immune activation while limiting compensatory tumor escape.
BRCA1 and GATA3 are critically involved in mammary gland development and tumorigenesis, yet clinical significance and relevance of these genes in breast cancer remains incompletely elucidated. In this study, we performed an integrated multi-database analysis to investigate the roles of BRCA1 and GATA3 in breast cancer. Analysis of multiple datasets revealed high mutation rates in both genes in breast cancer and high expression levels in ER-positive/luminal subtypes cancers relative to those in ER-negative/basal-like tumors. The expression of BRCA1 and GATA3 positively correlated with that of luminal markers but negatively correlated with that of basal-like markers and epithelial-mesenchymal transition transcription factors (EMT-TFs). Survival analyses indicated that high GATA3 expression conferred a favorable prognosis, whereas elevated BRCA1 expression predicted poor survival. This study provides valuable insights into the function and therapeutic implications of BRCA1 and GATA3 in breast cancer.
Helicobacter pylori driven gastric carcinogenesis contributes to stomach adenocarcinoma (STAD) through chronic inflammation, immune dysregulation, and tumour progression. This study aimed to identify H. pylori associated therapeutic targets and evaluate repurposed anticancer drugs through integrated computational and experimental approaches.
Differentially expressed genes from TCGA-STAD were filtered for H. pylori associated gene signatures using the Xena Browser. Gene expression, survival, network, and immune infiltration analysis were used for target prioritization. FDA-approved and clinical stage anticancer small molecules were screened by molecular docking, followed by 100-ns molecular dynamics (MD) simulations, principal component analysis (PCA), dynamic cross-correlation matrix (DCCM), and Prime MM-GBSA analysis. Experimental validation was performed in AGS cells using MTT, quantitative RT-PCR, and Western blotting.
Among 250 upregulated genes, 11 genes were associated with H. pylori positive STAD. TREM2 was prioritized based on overexpression, network connectivity, immune infiltration profile, and biological relevance, despite showing trend towards poor survival (HR = 1.20, p = 0.056). TREM2 expression was positively associated with immune-cell populations. Molecular docking identified Lerociclib as the top ranked compound interacting with TREM2 through hydrogen bonds involving Asn79, Ser81, and Asp104, along with hydrophobic and van der Waals interactions. MD, PCA, DCCM, and MM-GBSA analyses supported stable binding and coordinated residue dynamics. Lerociclib reduced cell viability and decreased TREM2 mRNA and protein expression in AGS cells.
This study identifies TREM2 as a promising therapeutic target in H. pylori associated STAD, while Lerociclib emerges as repurposed compound for TREM2. Further mechanistic and preclinical evaluation is required in gastric cancer.