Cytoplasmic PXR regulates glucose metabolism by binding mRNAs and modulating their stability.

ABSTRACT: Pregnane X receptor (PXR) is a nuclear receptor considered to be a master transcription factor of xenobiotic metabolism. Here, using enhanced ultraviolet crosslinking and immunoprecipitation, we show that PXR can bind mRNAs in different cancer cell lines and normal liver tissues. PXR-bound mRNAs include genes related to metabolic reprogramming and lipid metabolism. Separately from its known nuclear transcriptional function, cytoplasmic PXR binds and stabilizes mature mRNA containing C+G-enriched sequences through its zinc-finger domain. Mechanistically, cytoplasmic PXR interacts with RNH1, an RNase inhibitor, to regulate RNA stability. In colorectal cancer cells, cytoplasmic PXR facilitates glucose uptake by stabilizing SLC2A1 mRNA. This process further promotes cell proliferation and canc

SUBMITTER: Wang X 

PROVIDER: S-EPMC12781130 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature