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Abstract

In this research identified VPS72, which is a shared subunit of SRCAP and TRRAP-TIP60 complexes, to be overexpressed in hepatocellular carcinoma (HCC) and as one of the potential drivers of HCC pathogenesis. Functioning as a H2A.Z deposition chaperone, VPS72 has recently been shown to be involved in HCC growth. However, the detailed mechanisms by which VPS72 and H2A.Z participate in HCC development and progression remained elusive. I observed that VPS72 is localized primarily to the nucleolus, suggesting its potential role in ribosome biogenesis, which is essential for protein synthesis in rapidly dividing cancer cells. VPS72 overexpression in HCC cells led to increased levels of proteins involved in cell cycle progression, cell proliferation, cell division, and DNA repair. Additionally, VPS72 overexpression was associated with inhibited apoptosis and reduced CD8+ T cell infiltration. Furthermore, I found that VPS72 directly regulated the expression of its key downstream target, AURKB, by binding to its promoter and inducing chromatin remodeling. In terms of therapeutic implications, depletion of VPS72 in HCC cells reduced their growth and proliferation in in vitro experiments and in vivo tumor growth in mice. Overall, these findings suggest that VPS72/AURKB axis plays a critical role in HCC development and progression. Therefore, targeting VPS72 or its downstream effectors, like AURKB, holds promise for novel therapeutic strategies in HCC.