Bromodomain-containing protein 9 promotes hepatocellular carcinoma progression via activating the Wnt/β-catenin signaling pathway

Background: Epigenetic dysregulation participates in the initiation and progression of hepatocellular carcinoma (HCC). Bromodomain-containing protein 9 (BRD9) can identify acetylated lysine residues, contributing to several cancers. The function and molecular mechanism of BRD9 in HCC remain poorly understood. Methods: BRD9 levels in tissues and cells of HCC and normal liver were evaluated using bioinformatic analysis, real-time PCR, and western blot. BRD9's association with clinical outcomes was investigated via survival analyses. Biological behaviors and pathways related to BRD9 were predicted using gene set enrichment analysis. BRD9's role in proliferation was verified via cell counting kit 8, colony formation, and 5-Ethynyl-2'-deoxyuridine assays. Its role in the cell cycle and apoptosis was assessed using flow cytometry. The role of BRD9 in vivo was investigated using xenograft tumor models. A rescue assay was performed to investigate the molecular mechanism of BRD9. Results: BRD9 was markedly upregulated in HCC and higher BRD9 expression was associated with higher grade, advanced stage, greater tumor size, and poorer prognosis. BRD9 overexpression enhanced cell proliferation, cell cycle progress, but impeded cell apoptosis. BRD9 downregulation had the opposite effects. In vivo, BRD9 promoted xenograft tumor growth. Mechanistically, BRD9 activated Wnt/beta-catenin signaling, obstruction of which abrogated BRD9-mediated tumorigenesis. Conclusion: Increased BRD9 in HCC correlated with poor prognosis, which functioned via activating Wnt/beta-catenin signaling. Thus, BRD9 might be a promising biomarker and therapeutic target for patients with HCC.

Automated summary

The study found that in HCC, high expression of BRD9 was closely related to malignancy, tumor stage, tumor size, and prognosis. BRD9 promoted cell proliferation and tumor growth, and mediated its effects by activating the Wnt/beta-catenin signaling pathway.