Long noncoding RNA AGPG regulates PFKFB3-mediated tumor glycolytic reprogramming
Authors: Lin Feng
Yun Wang
De-Shen Wang
Chau-Wei Wong
Rui-Hua Xu
Jia Liu
Yun-Xin Lu
Ying Jin
Lei Miao
Dong-Liang Chen
Peng Huang
Dan Xie
Huai-Qiang Ju
Chao Ren
Mu-Sheng Zeng
Heng-Ying Pu
Dongxin Lin
Aifu Lin
Ze-Xian Liu
Qi-Nian Wu
Zixian Wang
Bo Li
Ming-Ming He
Journal: Nature Communications (2020)
Discipline: Multidisciplinary
Keywords: Tumor cells; metabolism remodeling; long noncoding RNAs; lncRNA; Actin Gamma 1 Pseudogene
Affiliations: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China., Department of Biochemistry and Molecular Biology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China., College of Life Sciences, Zhejiang University, Hangzhou, 310058, China., State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. ., Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, 510060, China. .

Abstract:  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. 

Retracted: No

PubPeer comments:
 Figure 2C appears to have a repeated image, after rotation. *** ![file] , 
 #1 90 deg rotation + stretching in one direction, then ended up perfect match ![file] , 
 We, the authors are terribly sorry for overlooking this mistake. While taking pictures for the colony formation assay, there were a lot of raw images that needed further processing like cropping and rotation, during that procedure, one picture in KYSE30 Ctrl group got mixed in KYSE150 shAGPG group. We then mistook it and used it as well. Thank you very much for pointing out this oversight of ours and we will immediately contact the editorial office of this mistake and make the necessary corrections by issuing a corrigendum. On a positive note, this result does not directly affect our hypothesis. Once more, we would like to express our most sincere gratitude for pointing out this oversight of ours, we will do our best to review all current work and publications in process and set up a new protocol for processing images to prevent it from happening again. , 
 u201cOn a positive note, this result does not directly affect our hypothesisu201d.... Doesnu2019t Nature Communications require all the raw data before publishing a paper ...? ,