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Long noncoding RNA AGPG regulates PFKFB3-mediated tumor glycolytic reprogramming.

Jia LiuZe-Xian LiuQi-Nian WuYun-Xin LuChau-Wei WongLei MiaoYun WangZixian WangYing JinMing-Ming HeChao RenDe-Shen WangDong-Liang ChenHeng-Ying PuLin FengBo LiDan XieMu-Sheng ZengPeng HuangAifu LinDongxin LinRui-Hua XuHuai-Qiang Ju
Published in: Nature communications (2020)
Tumor cells often reprogram their metabolism for rapid proliferation. The roles of long noncoding RNAs (lncRNAs) in metabolism remodeling and the underlying mechanisms remain elusive. Through screening, we found that the lncRNA Actin Gamma 1 Pseudogene (AGPG) is required for increased glycolysis activity and cell proliferation in esophageal squamous cell carcinoma (ESCC). Mechanistically, AGPG binds to and stabilizes 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). By preventing APC/C-mediated ubiquitination, AGPG protects PFKFB3 from proteasomal degradation, leading to the accumulation of PFKFB3 in cancer cells, which subsequently activates glycolytic flux and promotes cell cycle progression. AGPG is also a transcriptional target of p53; loss or mutation of TP53 triggers the marked upregulation of AGPG. Notably, inhibiting AGPG dramatically impaired tumor growth in patient-derived xenograft (PDX) models. Clinically, AGPG is highly expressed in many cancers, and high AGPG expression levels are correlated with poor prognosis, suggesting that AGPG is a potential biomarker and cancer therapeutic target.
Keyphrases
  • poor prognosis
  • cell cycle
  • cell proliferation
  • long noncoding rna
  • long non coding rna
  • signaling pathway
  • gene expression
  • squamous cell carcinoma
  • young adults
  • oxidative stress
  • quantum dots