ArticleNPJ precision oncology2026
ACACA modulates R-loop homeostasis to enhance lipid metabolism and microenvironmental interactions in ccRCC.
Article in NPJ precision oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- A mature tertiary lymphoid structure-associated spatial niche is inversely associated with ACC1-related lipid metabolism in neoadjuvant-treated hepatocellular carcinoma.Translational oncology · 2026Article
- Dietary Polyphenol Acteoside-Related Molecular Signatures in Clear Cell Renal Cell Carcinoma: Multi-Omics Profiling and Functional Validation of IMPDH1.Food science & nutrition · 2026Article
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
R-loops are dynamic nucleic acid structures implicated in genome regulation and instability, yet their contributions to the tumor microenvironment (TME) of clear cell renal cell carcinoma (ccRCC) remain unclear. Here, we integrated publicly available ccRCC transcriptomic and clinical datasets to quantify R-loop-associated activity using single-sample gene set enrichment analysis (ssGSEA) and develop a prognostic model using linear machine-learning algorithms. R-loop activity was elevated in advanced disease and associated with unfavorable outcomes. Among R-loop-related genes, ACACA was prioritized for its dominant contribution across multiple linear prognostic models, alongside its strong association with metabolic reprogramming. Single-cell transcriptomics showed relatively high ACACA expression in malignant cells that functioned as communication hubs with lipid metabolism-related signaling, and spatial transcriptomics confirmed preferential enrichment of ACACA within malignant regions. In vitro and xenograft experiments further demonstrated that ACACA promoted proliferation and migration and suppressed apoptosis, accompanied by reduced R-loop accumulation, enhanced fatty acid metabolism and improved mitochondrial function. Together, these findings identify ACACA as an R-loop-associated metabolic driver connecting genomic stress with lipid reprogramming and TME remodeling in ccRCC, supporting its potential as a prognostic biomarker and therapeutic target.
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Registered trials
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