SMYD5-BRD4 Interaction Drives Hepatocellular Carcinoma Progression: A Combined in Silico and Experimental Analysis

Background/Objectives: Hepatocellular carcinoma (LIHC) poses significant challenges due to limited targeted therapeutic options. This study investigates SMYD5, an oncogene implicated in the pathogenesis of LIHC, and its interaction with the BRD4 protein. Methods: We employed bioinformatics analyses alongside experimental validations to assess SMYD5 expression across various cancers, particularly LIHC. This included survival analysis, protein expression studies, and functional assays to understand the role of SMYD5 in LIHC progression. Results: Our findings demonstrate that SMYD5 expression is markedly elevated in LIHC tumor tissues compared to normal liver tissues. Moreover, high levels of SMYD5 correlate with poor overall survival and disease-free survival rates in LIHC patients. Functional assays indicate that the knockdown of SMYD5 significantly inhibits cell proliferation and increases Apoptosis in LIHC cell lines. Additionally, a notable interaction between SMYD5 and BRD4 was identified, suggesting a potential therapeutic target in the SMYD5-BRD4 axis. Conclusions: These findings collectively establish SMYD5 as a molecular driver in LIHC pathology and identify the SMYD5-BRD4 interaction axis as a promising therapeutic target for future drug development.

BRD4; LIHC; SMYD5; epigenetic; protein–protein interaction.