Integrating Single-Cell and Bulk RNA Sequencing Reveals the Malignant Phenotype of CBX4 in Prostate Cancer

Background: The expression pattern and functions of CBX4 in prostate cancers remain ambiguous. This study aims to investigate the performance of CBX4 in prostate cancer progression and preliminary inquiry potential mechanisms. Methods: The GEPIA data website was utilized to evaluate the expression patterns of CBX families and their correlations with prognosis. The "clusterprofiler" package was used for GSEA analysis. Seurat and CellChat package were used to analyze the single-cell expression profiles. The RT-qPCR, western blot and IHC staining were performed to detect the expression of CBX4 in prostate cancer tissues or cell lines. The cell functional experiments were performed, including MTT, colony formation assay, Transwell assay and scratch assay. Western blot was conducted to explore the regulation of CBX4 on EMT markers and PI3K/AKT pathway markers. Results: CBX4 was significantly up-regulated at tissue and cell levels in prostate cancer. High expression level of CBX4 was closely associated with advanced stage and poor prognosis. Of note, CBX4 was observed to promote immunosuppressive tumor environment via PDGF, VEGF, WNT signaling by cell-cell communications. In vitro experiments confirmed the expression level. Cell function and western blot proved the down-regulation of CBX4 dramatically inhibited the proliferation, invasion and migration of prostate cancer cells by targeting PI3K/AKT signaling. Conclusion: CBX4 might serve as a potential oncogene in prostate cancer progression. This study provides a new target for the treatment of prostate cancer.