Clinical and Translational Medicine (Dec 2023)

RFX6 facilitates aerobic glycolysis‐mediated growth and metastasis of hepatocellular carcinoma through targeting PGAM1

  • Zhiyu Qiu,
  • Chenwei Wang,
  • Pinzhu Huang,
  • Yichuan Yuan,
  • Yunxing Shi,
  • Zhu Lin,
  • Zhenkun Huang,
  • Dinglan Zuo,
  • Jiliang Qiu,
  • Wei He,
  • Jingxian Shen,
  • Yi Niu,
  • Yunfei Yuan,
  • Binkui Li

DOI
https://doi.org/10.1002/ctm2.1511
Journal volume & issue
Vol. 13, no. 12
pp. n/a – n/a

Abstract

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Abstract Background Hepatocellular carcinoma (HCC) cells undergo reprogramming of glucose metabolism to support uncontrolled proliferation, of which the intrinsic mechanism still merits further investigation. Although regulatory factor X6 (RFX6) is aberrantly expressed in different cancers, its precise role in cancer development remains ambiguous. Methods Microarrays of HCC tissues were employed to investigate the expression of RFX6 in tumour and adjacent non‐neoplastic tissues. Functional assays were employed to explore the role of RFX6 in HCC development. Chromatin immunoprecipitation, untargeted metabolome profiling and sequencing were performed to identify potential downstream genes and pathways regulated by RFX6. Metabolic assays were employed to investigate the effect of RFX6 on glycolysis in HCC cells. Bioinformatics databases were used to validate the above findings. Results HCC tissues exhibited elevated expression of RFX6. High RFX6 expression represented as an independent hazard factor correlated to poor prognosis in patients with HCC. RFX6 deficiency inhibited HCC development in vitro and in vivo, while its overexpression exerted opposite functions. Mechanistically, RFX6 bound to the promoter area of phosphoglycerate mutase 1 (PGAM1) and upregulated its expression. The increased PGAM1 protein levels enhanced glycolysis and further promoted the development of HCC. Conclusions RFX6 acted as a novel driver for HCC development by promoting aerobic glycolysis, disclosing the potential of the RFX6–PGAM1 axis for therapeutic targeting.

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