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<p>This study aims to explore biomarkers linked to the progression from non-alcoholic fatty liver disease (NAFLD) to hepatocellular carcinoma (HCC) and their therapeutic potential. Using bioinformatics, we identified key differentially expressed genes from various databases, focusing on genes related to NAFLD, non-alcoholic steatohepatitis, liver cirrhosis, and HCC. Among the upregulated genes, baculoviral IAP repeat containing 5 (BIRC5), cyclin B1 (CCNB1), cyclin-dependent kinase 1 (CDK1), and DNA topoisomerase II alpha (TOP2A) were found to be significant. In vivo and in vitro models of NAFLD and clinical HCC samples validated BIRC5 as a critical regulator in the disease progression. Functional assays revealed that knocking down BIRC5 alleviated fatty acid-induced liver damage and mitochondrial dysfunction in NAFLD models, while also inhibiting HCC cells proliferation and migration, further leading to mitochondrial dysfunction. YM155 (a specific BIRC5 inhibitor) also confirmed the previous experimental results. Then we performed experiments using BIRC5 overexpression plasmid. BIRC5 overexpression exacerbated hepatic steatosis and mitochondrial function in free fatty acid (FFA) -induced AML12 hepatocytes, and enhanced HCC cells proliferation, migration, and invasion. These findings highlight BIRC5 as a pivotal driver in the NAFLD-HCC transition, mediating metabolic dysfunction and malignant transformation. This study proposes BIRC5 as a therapeutic target and diagnostic biomarker, offering perspectives for HCC diagnosis and treatment of HCC. These results underscore the importance of BIRC5 in halting NAFLD-HCC progression and provide valuable insights for future clinical applications.</p> Graphical Abstract <p></p>

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From bioinformatics to clinical translation: BIRC5 as a pivotal diagnostic biomarker and therapeutic target for NAFLD-driven HCC

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月10日

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  • Yushu Huang,
  • He He,
  • Xueqing Xia,
  • Lifang Jiang,
  • Qifeng Peng,
  • Qingfeng Du,
  • Yanting You

摘要

This study aims to explore biomarkers linked to the progression from non-alcoholic fatty liver disease (NAFLD) to hepatocellular carcinoma (HCC) and their therapeutic potential. Using bioinformatics, we identified key differentially expressed genes from various databases, focusing on genes related to NAFLD, non-alcoholic steatohepatitis, liver cirrhosis, and HCC. Among the upregulated genes, baculoviral IAP repeat containing 5 (BIRC5), cyclin B1 (CCNB1), cyclin-dependent kinase 1 (CDK1), and DNA topoisomerase II alpha (TOP2A) were found to be significant. In vivo and in vitro models of NAFLD and clinical HCC samples validated BIRC5 as a critical regulator in the disease progression. Functional assays revealed that knocking down BIRC5 alleviated fatty acid-induced liver damage and mitochondrial dysfunction in NAFLD models, while also inhibiting HCC cells proliferation and migration, further leading to mitochondrial dysfunction. YM155 (a specific BIRC5 inhibitor) also confirmed the previous experimental results. Then we performed experiments using BIRC5 overexpression plasmid. BIRC5 overexpression exacerbated hepatic steatosis and mitochondrial function in free fatty acid (FFA) -induced AML12 hepatocytes, and enhanced HCC cells proliferation, migration, and invasion. These findings highlight BIRC5 as a pivotal driver in the NAFLD-HCC transition, mediating metabolic dysfunction and malignant transformation. This study proposes BIRC5 as a therapeutic target and diagnostic biomarker, offering perspectives for HCC diagnosis and treatment of HCC. These results underscore the importance of BIRC5 in halting NAFLD-HCC progression and provide valuable insights for future clinical applications.

Graphical Abstract