USF1‐mediated ALKBH5 stabilizes FLII mRNA in an m6A‐YTHDF2‐dependent manner to repress glycolytic activity in prostate adenocarcinoma

Jul 26, 2023Molecular carcinogenesis

USF1 helps preserve FLII mRNA through m6A-related pathways to reduce sugar metabolism in prostate cancer

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Abstract

Low levels of USF1 are correlated with an unfavorable prognosis in prostate adenocarcinoma (PRAD).

  • Bioinformatics analyses indicated that USF1 is poorly expressed in PRAD.
  • Clinical samples of PRAD showed a significant correlation between low USF1 levels and poor patient outcomes.
  • Artificial upregulation of USF1 repressed glycolytic activity and reduced cell growth and metastasis in PRAD cells, both in vitro and in vivo.
  • USF1 was found to activate the ALKBH5 promoter, which in turn stabilized the FLII mRNA.
  • Silencing of ALKBH5 or FLII reversed the effects of USF1, restoring glycolysis, cell proliferation, and invasion in PRAD cells.
  • The findings suggest that USF1 may play a role in repressing glycolysis and tumor progression in PRAD through the ALKBH5-FLII axis.

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Full Text

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