Liu Zihao, Liu Yang, Fu Zhinan, Huang Hua, Wang Runpeng, Wang Zhun, Peng Shuanghe, Wang Jiahao, Fang Ziqi, Liu Liwei, Chen Ruibing, Wang Yong
Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, China.
Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin, 300211, China.
J Cancer. 2025 Jul 28;16(11):3525-3536. doi: 10.7150/jca.115613. eCollection 2025.
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. 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. 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. 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. CBX4 might serve as a potential oncogene in prostate cancer progression. This study provides a new target for the treatment of prostate cancer.
CBX4在前列腺癌中的表达模式和功能仍不明确。本研究旨在探讨CBX4在前列腺癌进展中的表现,并初步探究其潜在机制。利用GEPIA数据网站评估CBX家族的表达模式及其与预后的相关性。使用“clusterprofiler”软件包进行基因集富集分析(GSEA)。利用Seurat和CellChat软件包分析单细胞表达谱。采用逆转录定量聚合酶链反应(RT-qPCR)、蛋白质免疫印迹法(western blot)和免疫组化(IHC)染色检测前列腺癌组织或细胞系中CBX4的表达。进行细胞功能实验,包括MTT实验、集落形成实验、Transwell实验和划痕实验。通过蛋白质免疫印迹法探究CBX4对上皮-间质转化(EMT)标志物和磷脂酰肌醇-3激酶/蛋白激酶B(PI3K/AKT)信号通路标志物的调控作用。在前列腺癌的组织和细胞水平上,CBX4均显著上调。CBX4的高表达水平与晚期和不良预后密切相关。值得注意的是,通过细胞间通讯观察到CBX4可通过血小板衍生生长因子(PDGF)、血管内皮生长因子(VEGF)、Wnt信号通路促进免疫抑制性肿瘤环境。实验证实了表达水平。细胞功能和蛋白质免疫印迹法证明,下调CBX4可通过靶向PI3K/AKT信号通路显著抑制前列腺癌细胞的增殖、侵袭和迁移。CBX4可能是前列腺癌进展中的一个潜在癌基因。本研究为前列腺癌的治疗提供了一个新靶点。