例如:"lncRNA", "apoptosis", "WRKY"

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

Nat Commun. 2018 Apr 16;9(1):1480
Liang Zhou 1 , Yinghui Wang 1 , Meijuan Zhou 1 , Ying Zhang 1 , Pengfei Wang 1 , Xiaoxing Li 2 , Jing Yang 2 , Hongmei Wang 2 , Zhenhua Ding 3
Liang Zhou 1 , Yinghui Wang 1 , Meijuan Zhou 1 , Ying Zhang 1 , Pengfei Wang 1 , Xiaoxing Li 2 , Jing Yang 2 , Hongmei Wang 2 , Zhenhua Ding 3
+ et al

[No authors listed]

Author information
  • 1 Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, 510515, Guangzhou, China.
  • 2 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 510060, Guangzhou, China.
  • 3 Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, 510515, Guangzhou, China. dingzh@smu.edu.cn.

摘要


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.