2. Academic Validation
  3. USF1-induced RPS6KB2 activation influences aggressive phenotype in B-cell non-Hodgkin lymphoma

USF1-induced RPS6KB2 activation influences aggressive phenotype in B-cell non-Hodgkin lymphoma

  • Hum Cell. 2025 Aug 31;38(5):154. doi: 10.1007/s13577-025-01284-x.
Zhaoyu Liu # 1,  Xiang Song # 2,  Zhuang Liu 3,  Xiaoyu He 2,  Hong Gao 4,  Xunru Liu 3
Affiliations

Affiliations

  • 1 Department of Oncology, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Xinghualing District, Taiyuan, 030001, Shanxi, People's Republic of China. lunerheart009@126.com.
  • 2 Department of Oncology, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Xinghualing District, Taiyuan, 030001, Shanxi, People's Republic of China.
  • 3 Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, People's Republic of China.
  • 4 Department of Digestion, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, People's Republic of China.
  • # Contributed equally.
PMID: 40886264 DOI: 10.1007/s13577-025-01284-x
Abstract

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.

Keywords

B-cell non-Hodgkin lymphoma; Human double minute 2; P53; Protein kinase B; Ribosomal protein S6 kinase B2; Upstream stimulatory factor 1.

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