Multi-omics analysis of transcriptome and proteome reveals that BAZ1A and BAZ2A have common and individual regulatory roles in hepatocellular carcinoma

Abstract

This study employs an integrative multi-omics approach to elucidate the complex regulatory roles of BAZ1A and BAZ2A, subunits of the ISWI chromatin remodeling complexes, in hepatocellular carcinoma (HCC). Utilizing siRNA-mediated knockdown, combined with high-throughput RNA sequencing and mass spectrometry, the researchers reveal distinct and overlapping functions of BAZ1A and BAZ2A in both transcriptional and proteomic regulation. The findings indicate that BAZ1A is primarily involved in ribosomal biogenesis and nucleolar function, while BAZ2A exerts significant influence on cell cycle progression and DNA repair mechanisms. Through a comprehensive analysis of the transcriptome and proteome following gene knockdown, the study highlights the intricate interplay between these two subunits, which contributes to the pathogenesis of HCC. This integrated approach not only uncovers their differential impact on gene expression and protein abundance but also reveals their involvement in alternative splicing events. Additionally, potential downstream targets and associated signaling pathways are identified, providing valuable insights into the molecular mechanisms underlying HCC development. The distinct roles of BAZ1A and BAZ2A in various cellular processes, along with their differential effects on gene and protein regulation, position them as promising therapeutic targets. These results offer new perspectives for understanding the molecular basis of HCC and suggest potential avenues for targeted therapies.