ReviewPharmaceutical research2026
Regulatory Roles of Long Non-Coding RNAs in Methotrexate Pharmacology: Mechanistic and Translational Insights.
Review in Pharmaceutical research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
1 citing paper in PubMed.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMethotrexate (MTX) remains a cornerstone therapy in autoimmune diseases and oncology; however, substantial interindividual variability in efficacy and toxicity persists. While variability in MTX pharmacokinetics (PK) and pharmacodynamics (PD) has been linked to transporters, folate-cycle enzymes, and intracellular polyglutamate accumulation, the contribution of long non-coding RNAs (lncRNAs) as regulatory modifiers of these processes is not yet systematically defined.
objectiveTo synthesize current evidence on lncRNA-mediated regulation of MTX response and to organize these interactions within a pharmacology-centered mechanistic framework.
methodsA narrative, mechanism-oriented review was conducted integrating preclinical, translational, and computational studies evaluating lncRNA involvement in MTX-related pathways across immune-mediated diseases and cancer.
resultslncRNAs were found to intersect with MTX pharmacology across four principal mechanistic nodes: (1) regulation of drug transport and intracellular retention (e.g., modulation of ABC transporters); (2) control of folate-axis targets and compensatory metabolic pathways (e.g., DHFR and TYMS regulation); (3) modulation of adenosine-mediated immunoregulation and NF-κB signaling, with lincRNA-p21 representing the most mechanistically supported example in rheumatoid arthritis; and (4) orchestration of stress-adaptive and survival pathways influencing antifolate resistance (e.g., PI3K-AKT-mTOR and apoptosis networks). However, most evidence derives from in vitro or computational studies, with limited integration of lncRNA perturbation and quantitative PK metrics such as intracellular MTX-polyglutamate levels.
conclusionslncRNAs function as context-dependent modulators of MTX PK/PD processes rather than primary drug targets. Current evidence is heterogeneous, future studies integrating functional genomics, PK measurements, and prospective clinical validation are required to establish lncRNAs as predictive biomarkers or therapeutic targets in MTX precision pharmacology.
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Registered trials
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