USF1 promotes growth and glycolysis in acute myeloid leukemia cells.

Abstract

Acute myeloid leukemia (AML) is a hematological malignancy characterized by impaired hematopoiesis and aggressive progression, with limited treatment options and poor prognosis, especially in elderly patients. Metabolic reprogramming, particularly enhanced glycolysis, is a hallmark of AML and contributes to disease progression and therapy resistance. Upstream stimulatory factor 1 (USF1) regulates metabolism, the cell cycle, and oncogenesis in solid tumors, whereas its role in AML remains unclear. Herein, we investigated the role and underlying mechanism of USF1 in regulating USP25 transcription and promoting AML progression. We found that USF1 was highly expressed in AML samples and cell lines, and its elevated expression was associated with poor prognosis. Functional assays showed that USF1 promoted AML cell growth and glycolysis while inhibiting apoptosis. Mechanistically, USF1 directly bound to the USP25 promoter, enhancing its transcription. Knockdown of USP25 reversed the tumor-promoting effects of USF1. Moreover, in vivo studies demonstrated that silencing USF1 significantly inhibited tumor growth. In conclusion, USF1 promotes AML cell growth and glycolysis through the transcriptional activation of USP25, thereby identifying the USF1-USP25 axis as a potential therapeutic target for AML.