ArticleArchives of toxicology2025
Long non-coding RNA LINC02499 regulates the expression of CYP3A5 in human liver cells.
Article in Archives of toxicology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors.
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Abstract
Cytochrome P450 3A5 (CYP3A5) is a critical drug-metabolizing enzyme in human hepatocytes, playing a key role in the metabolism of various clinically relevant drugs, with considerable variability in gene expression across individuals. Long non-coding RNAs (lncRNAs) are likely to be important regulators within the CYP3A5 regulatory network in the liver. In this study, we employed a computational approach to estimate Sobol's sensitivity indices (SSI) under generalized linear models, applied to liver RNA expression microarray data (GTEx v8). The SSI-based analysis revealed that the long non-coding RNA LINC02499 exhibits the highest SSI value in relation to CYP3A5 expression in the liver. Furthermore, we conducted a comprehensive evaluation of LINC02499's biological characteristics and confirmed its regulatory role in CYP3A5 expression through real-time quantitative PCR and Western blotting experiments at the cellular level. We also demonstrated the direct interaction between miR-329-5p and both LINC02499 and CYP3A5 mRNA using dual-luciferase reporter assays and electrophoretic mobility shift assays (EMSA). In conclusion, our findings outline a regulatory network in which LINC02499 functions as a molecular sponge, mitigating the post-transcriptional inhibitory effect of miR-329-5p on CYP3A5 expression.
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