Wei Shanshan, Sun Jie, Wen Jiahao, Yu Jianing, Xuan Yixuan, Huang Jingyu, Yang Jie, Zhang Jianfeng
Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Department of Hematological Oncology and Pediatric Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China.
PLoS One. 2025 May 21;20(5):e0323965. doi: 10.1371/journal.pone.0323965. eCollection 2025.
Steroid 5α-reductase 3 (SRD5A3) is an important molecule involved in glycosylation and steroid hormone formation and is highly expressed in most tumors. However, The role of SRD5A3 in B-cell non-Hodgkin lymphoma (B-NHL) and its mechanism are unknown.
We used a multi-omics database to explore the expression and prognostic significance of SRD5A3 in various tumors, including B-NHL. We established SRD5A3 high- and low-expression B-NHL cell lines to test the effects of SRD5A3 on cell proliferation and apoptosis in vitro, and to analyze the signaling pathways associated with the effects of SRD5A3 on B-NHL.
We found that SRD5A3 was highly expressed in most tumors, including B-NHL, and was more highly expressed in patients age ≥60 years, high levels of LDH, stage III-IV, non-GCB subtype, and extra-nodal invasion. Survival analysis showed that high SRD5A3 expression predicted poorer overall survival (OS). Further experiments showed that SRD5A3 high expression promoted B-NHL growth and attenuates apoptosis, conversely, SRD5A3 low expression inhibited B-NHL growth and promoted apoptosis. Western blot assay showed SRD5A3 promotes B-NHL cells growth by regulating the PI3K-AKT signaling pathway.
Our findings suggest that SRD5A3 exerts its oncogenic effects by regulating the PI3K-AKT pathway, may serve as a potential biomarker and therapeutic target for B-NHL, providing information for clinical decision-making.
类固醇5α-还原酶3(SRD5A3)是参与糖基化和类固醇激素形成的重要分子,在大多数肿瘤中高表达。然而,SRD5A3在B细胞非霍奇金淋巴瘤(B-NHL)中的作用及其机制尚不清楚。
我们使用多组学数据库探索SRD5A3在包括B-NHL在内的各种肿瘤中的表达及预后意义。我们建立了SRD5A3高表达和低表达的B-NHL细胞系,以测试SRD5A3对体外细胞增殖和凋亡的影响,并分析与SRD5A3对B-NHL作用相关的信号通路。
我们发现SRD5A3在包括B-NHL在内的大多数肿瘤中高表达,在年龄≥60岁、乳酸脱氢酶水平高、III-IV期、非生发中心B细胞(GCB)亚型和结外侵犯的患者中表达更高。生存分析表明,SRD5A3高表达预示总体生存(OS)较差。进一步实验表明,SRD5A3高表达促进B-NHL生长并减弱凋亡,相反,SRD5A3低表达抑制B-NHL生长并促进凋亡。蛋白质印迹分析表明,SRD5A3通过调节PI3K-AKT信号通路促进B-NHL细胞生长。
我们的研究结果表明,SRD5A3通过调节PI3K-AKT通路发挥致癌作用,可能作为B-NHL的潜在生物标志物和治疗靶点,为临床决策提供信息。