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

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-1? and its downstream glycolytic regulators, HK2, GLUT1 and PDK1. Mechanistic studies show that HOXA9-CRIP2 interaction at glycolytic gene promoters impeds HIF-1? binding, repressing gene expression in trans. Our results reveal a miR-365-HOXA9-HIF-1? regulatory axis that contributes to the enhanced glycolysis in cSCC development and may represent an intervention target for cSCC therapy.

SUBMITTER: Zhou L

PROVIDER: S-EPMC5902613 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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

Zhou Liang L Wang Yinghui Y Zhou Meijuan M Zhang Ying Y Wang Pengfei P Li Xiaoxing X Yang Jing J Wang Hongmei H Ding Zhenhua Z

Nature communications 20180416 1

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, ...[more]

PMID: 29662084

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