Abstract
Mitochondrial ribosomal proteins of the large subunit (MRPLs) are critical for mitochondrial function and cellular energy metabolism. However, the role of the MRPL family in hepatocellular carcinoma (HCC) remains poorly understood. Here, we leveraged The Cancer Genome Atlas (TCGA) liver cancer data to develop a subtype classification and prognostic model based on the MRPL family genes, identifying MRPL37 as a key gene associated with HCC progression. Clinically, MRPL37 upregulation is associated with HCC progression and poor prognosis. Functionally, MRPL37 knockdown significantly inhibits HCC cell proliferation, disrupts cell cycle progression, and induces apoptosis in vitro. In vivo, silencing MRPL37 reduces tumor growth in both xenograft and spontaneous liver cancer models. Mechanistically, MRPL37 regulates mitochondrial protein synthesis, influencing key metabolic pathways and mitochondrial function, including oxidative phosphorylation. Our results suggest MRPL37 as a critical regulator of energy metabolism in HCC, highlighting its potential as a therapeutic target for liver cancer.