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HOXA9 inhibits HIF-1α-mediated glycolysis through interacting with CRIP2 to repress cutaneous squamous cell carcinoma development

Author

Listed:
  • Liang Zhou

    (Southern Medical University)

  • Yinghui Wang

    (Southern Medical University)

  • Meijuan Zhou

    (Southern Medical University)

  • Ying Zhang

    (Southern Medical University)

  • Pengfei Wang

    (Southern Medical University)

  • Xiaoxing Li

    (Sun Yat-sen University Cancer Center)

  • Jing Yang

    (Sun Yat-sen University Cancer Center)

  • Hongmei Wang

    (Sun Yat-sen University Cancer Center)

  • Zhenhua Ding

    (Southern Medical University)

Abstract

Glycolytic reprogramming is a typical feature of many cancers; however, key regulators of glucose metabolism reengineering are poorly understood, especially in cutaneous squamous cell carcinoma (cSCC). Here, Homeobox A9 (HOXA9), a direct target of onco-miR-365, is identified to be significantly downregulated in cSCC tumors and cell lines. HOXA9 acts as a tumor suppressor and inhibits glycolysis in cSCC in vitro and in vivo by negatively regulating HIF-1α and its downstream glycolytic regulators, HK2, GLUT1 and PDK1. Mechanistic studies show that HOXA9-CRIP2 interaction at glycolytic gene promoters impeds HIF-1α binding, repressing gene expression in trans. Our results reveal a miR-365-HOXA9-HIF-1α regulatory axis that contributes to the enhanced glycolysis in cSCC development and may represent an intervention target for cSCC therapy.

Suggested Citation

  • Liang Zhou & Yinghui Wang & Meijuan Zhou & Ying Zhang & Pengfei Wang & Xiaoxing Li & Jing Yang & Hongmei Wang & Zhenhua Ding, 2018. "HOXA9 inhibits HIF-1α-mediated glycolysis through interacting with CRIP2 to repress cutaneous squamous cell carcinoma development," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03914-5
    DOI: 10.1038/s41467-018-03914-5
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    Cited by:

    1. Sandro Goruppi & Andrea Clocchiatti & Giulia Bottoni & Emery Cicco & Min Ma & Beatrice Tassone & Victor Neel & Shadhmer Demehri & Christian Simon & G. Paolo Dotto, 2023. "The ULK3 kinase is a determinant of keratinocyte self-renewal and tumorigenesis targeting the arginine methylome," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

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