LARP1 drives steatosis to hepatocellular carcinoma progression in MASH mouse models

Background: This study focuses on the role of an RNA binding protein, La-related protein 1 or LARP1 in progression of metabolic dysfunction–associated steatotic liver disease (MASLD). A knockout mouse model of the S-adenosylmethionine (SAMe) synthetic enzyme, methionine adenosyltransferase 1A (Mat1a-KO) spontaneously develops MASH and progresses to HCC. We discovered that LARP1 is strongly induced in Mat1a KO during the MASH stage (Ramani 2022, PMC8766892). RNA‑sequencing from LARP1‑overexpressing liver cancer cells and from Larp1‑silenced Mat1a KOs revealed that LARP1 regulates mRNAs controlling key metabolic pathways, including peroxisomal β‑oxidation (Sirtuin 5, SIRT5), aerobic glycolysis (c‑MYC), and oxidative phosphorylation/mitochondrial ribosomal proteins (MRPL13, MRPL50, MRPL59). This dataset is bulk RNA sequencing data from the above studies. Our findings from RNA sequencing reveal a novel role for LARP1 in regulating metabolic pathways associated with MASLD progression through its dysregulation of key mRNAs involved in these pathways.