Liu Zhaoyu, Song Xiang, Liu Zhuang, He Xiaoyu, Gao Hong, Liu Xunru
Department of Oncology, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Xinghualing District, Taiyuan, 030001, Shanxi, People's Republic of China.
Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, People's Republic of China.
Hum Cell. 2025 Aug 31;38(5):154. doi: 10.1007/s13577-025-01284-x.
B-cell non-Hodgkin lymphoma (B-NHL) is a diverse group of aggressive lymphoid malignancies characterized by its molecular complexity. This study investigated the role of the upstream stimulatory factor 1 (USF1)-ribosomal protein S6 kinase B2 (RPS6KB2) axis in B-NHL progression through the AKT/HDM2 (also known as MDM2)/p53 signaling pathway. Using data from the GEO database, RPS6KB2 was identified to be overexpressed in B-NHL, which was confirmed by RT-qPCR, immunohistochemistry, and western blotting in both B-NHL tissues and cell lines. Functional studies revealed that RPS6KB2 knockdown reduced cell proliferation, migration, and tumor growth, while promoting apoptosis, effects that could be reversed by the AKT activator SC79. Bioinformatics analysis showed that USF1 activated the transcription of RPS6KB2 by directly binding to its promoter region. USF1 downregulation inhibited B-NHL progression, which was rescued by RPS6KB2 overexpression. These findings suggest that the USF1-RPS6KB2 axis contributes to B-NHL progression by activating the AKT/HDM2/p53 pathway.
B细胞非霍奇金淋巴瘤（B-NHL）是一组异质性侵袭性淋巴恶性肿瘤，其特征在于分子复杂性。本研究通过AKT/HDM2（也称为MDM2）/p53信号通路，研究了上游刺激因子1（USF1）-核糖体蛋白S6激酶B2（RPS6KB2）轴在B-NHL进展中的作用。利用GEO数据库的数据，RPS6KB2被鉴定为在B-NHL中过表达，这在B-NHL组织和细胞系中通过RT-qPCR、免疫组织化学和蛋白质印迹得到证实。功能研究表明，RPS6KB2敲低降低了细胞增殖、迁移和肿瘤生长，同时促进了细胞凋亡，而AKT激活剂SC79可逆转这些作用。生物信息学分析表明，USF1通过直接结合其启动子区域激活RPS6KB2的转录。USF1下调抑制了B-NHL进展，而RPS6KB2过表达可使其恢复。这些发现表明，USF1-RPS6KB2轴通过激活AKT/HDM2/p53通路促进B-NHL进展。
