This new review article highlights the critical role of ribosome biogenesis in liver health and disease progression. As the center of protein synthesis, ribosomes influence liver regeneration, hepatitis C virus (HCV) infection, nonalcoholic fatty liver disease (NAFLD), liver fibrosis, cirrhosis, and hepatocellular carcinoma. The article explores how disruptions in this process contribute to disease and how targeted therapies could offer new treatment avenues.

Ribosome biogenesis is a highly coordinated process that begins in the nucleolus and concludes in the cytoplasm, involving ribosomal RNA, ribosomal proteins, and biogenesis factors. It directly influences the liver’s ability to repair itself after injury. In conditions like HCV infection, viral replication is dependent on host ribosomes, making ribosome-targeting therapies a promising strategy. Similarly, in NAFLD, excessive lipogenesis is linked to ribosomal activity, highlighting a potential metabolic intervention point.

Chronic liver diseases such as fibrosis and cirrhosis arise when excessive extracellular matrix deposition and scarring impair liver function. The activation of hepatic stellate cells, driven by abnormal ribosome biogenesis, plays a central role in these diseases. Understanding this connection opens possibilities for new therapeutic targets that can halt or reverse disease progression.
In hepatocellular carcinoma, an overactive ribosome biogenesis process fuels tumor growth, making it a prime target for drug development. Pharmacological inhibitors that disrupt rRNA synthesis or ribosomal protein function are under investigation, with early findings suggesting their potential effectiveness in slowing tumor progression.

The review also discusses drugs currently being explored to exploit ribosome biogenesis in cancer treatment. Compounds such as CX-5461, which inhibits RNA polymerase I, have shown promise in preclinical studies. Combining ribosome-targeting drugs with existing chemotherapies may improve outcomes for patients with advanced liver diseases.

By deciphering the molecular pathways linking ribosome biogenesis and liver pathology, researchers aim to develop targeted, effective treatments for chronic liver diseases and liver cancer.

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Reference
Wei Luo, Jing Zhou, Yongmin Yan, Xuezhong Xu, Ribosome biogenesis: A central player in liver diseases,
Genes & Diseases, Volume 12, Issue 5, 2025, 101512, https://doi.org/10.1016/j.gendis.2025.101512

Funding Information:
National Natural Science Foundation of China 82272421
Changzhou's 14th Five-Year Plan Project to Train High-Level Health Professionals (Jiangsu, China) 2022CZLJ027
Changzhou Special Program for the Introduction of Foreign Talents CQ20240052
Open project of Jiangsu Provincial Key Laboratory of Key Laboratory of Laboratory Medicine JSKLM-Z-2024-001
Open project of Jiangsu Provincial Key Laboratory of Key Laboratory of Laboratory Medicine JSKLM-Z-2024-002