Fan Shicheng, Xia Zhongyou, Liu Weijia, Zhu Yuanquan, Liu Xiaodong, Gu Peng, Cui Qingpeng
Department of Urology, The Third People's Hospital of Yunnan Province, Kunming, Yunnan, China.
Department of Urology, Beijing Anzhen Nanchong Hospital, Capital Medical University & Nanchong Central Hospital, Nanchong, Sichuan, China.
FASEB J. 2025 Apr 15;39(7):e70508. doi: 10.1096/fj.202403129RR.
STEAP4 manifested differential expression and aberrant methylation in prostate cancer (PCa). Therefore, this study proposed to explore the effect of STEAP4 on the PCa malignant phenotype in vivo and in vitro and the possible molecular mechanisms using RNA-seq. The expression of STEAP4 in PCa and its prognostic and diagnostic value was identified using bioinformatics. After exogenous modulation of STEAP4, the effect of STEAP4 on the malignant phenotype of PCa cells was examined using functional assays and nude mouse tumor models. The STEAP4-related differentially expressed genes (DEGs) and the hub genes were characterized using RNA-seq in conjunction with bioinformatics. STEAP4 exhibited high expression in PCa tissues from TCGA-PRAD and GEO datasets (GSE179321, GSE229904, and GSE237995), which predicted lower survival of patients. The STEAP4-associated nomogram model and diagnostic ROC curve had excellent predictive performance (AUC = 0.814). STEAP4 was overexpressed in PCa tissues and cells. Knockdown of STEAP4 effectively decreased the viability, number of invading cells, and wound healing of PCa cells and increased apoptosis. Overexpression of STEAP4 showed the opposite pattern. RNA-seq revealed that knockdown of STEAP4 resulted in 234 DEGs in PCa cells. FGF17, KCNQ2, PDGFRB, and NOTCH4 are hub genes in DEGs. Notably, NOTCH4 was likewise overexpressed in PCa tissues and cells and was regulated by STEAP4. In in vitro experiments, overexpression of NOTCH4 facilitated PCa cell proliferation, migration, and invasion, which was limited by knockdown of STEAP4. In in vivo experiments, overexpression of STEAP4 exacerbated PCa tumor burden, which was rescued by knockdown of NOTCH4. STEAP4 is a valid biomarker for predicting prognosis and diagnosis of PCa patients. STEAP4 contributes to PCa growth, migration, and invasion by upregulating NOTCH4.
STEAP4在前列腺癌（PCa）中表现出差异表达和异常甲基化。因此，本研究旨在利用RNA测序探索STEAP4在体内和体外对PCa恶性表型的影响以及可能的分子机制。使用生物信息学鉴定了STEAP4在PCa中的表达及其预后和诊断价值。对外源调节STEAP4后，通过功能测定和裸鼠肿瘤模型检测STEAP4对PCa细胞恶性表型的影响。结合生物信息学，使用RNA测序对与STEAP4相关的差异表达基因（DEGs）和枢纽基因进行了表征。在TCGA-PRAD和GEO数据集（GSE179321、GSE229904和GSE237995）的PCa组织中，STEAP4表达较高，这预示着患者的生存率较低。与STEAP4相关的列线图模型和诊断ROC曲线具有出色的预测性能（AUC = 0.814）。STEAP4在PCa组织和细胞中过表达。敲低STEAP4可有效降低PCa细胞的活力、侵袭细胞数量和伤口愈合能力，并增加细胞凋亡。STEAP4过表达则表现出相反的模式。RNA测序显示，敲低STEAP4导致PCa细胞中有234个DEGs。FGF17、KCNQ2、PDGFRB和NOTCH4是DEGs中的枢纽基因。值得注意的是，NOTCH4在PCa组织和细胞中同样过表达，并受STEAP4调控。在体外实验中，NOTCH4过表达促进了PCa细胞的增殖、迁移和侵袭，而STEAP4敲低则限制了这些作用。在体内实验中，STEAP4过表达加剧了PCa肿瘤负担，而NOTCH4敲低则可缓解这一情况。STEAP4是预测PCa患者预后和诊断的有效生物标志物。STEAP4通过上调NOTCH4促进PCa的生长、迁移和侵袭。
