Mitochondria-specific targeting of noncanonical <i>EGR1</i> ntmRNA-coordinated mitophagy receptor BNIP3 homodimerization disrupts mitochondrial metabolism and suppresses hepatocellular carcinoma growth <i>in vitro</i> and <i>in vivo</i>.

ABSTRACT: Background: Hypoxia-driven metabolic reprogramming is a hallmark of hepatocellular carcinoma (HCC) and depends critically on mitochondrial signaling. We sought to identify RNA-based molecular factors that orchestrate the hypoxia-mitochondria crosstalk and regulate metabolic adaptation in HCC cells. Methods: An integrated mtRNA-seq and mitochondria-specific LwaCas13a-BN-MLS RNA targeting approach was employed to profile RNA molecules aberrantly enriched in HCC mitochondria. Mitophagy was assessed via mt-Keima assay, immunofluorescence, transmission electron microscopy, and Western blotting of key autophagic markers. RNA-protein interactions were examined using RNA immunoprecipitation (RIP), electrophoretic mobility shift assays (EMSA), and computational structural modeling.

SUBMITTER: Li Y 

PROVIDER: S-EPMC12680496 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature