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Title:
Long noncoding RNA AGPG regulates PFKFB3-mediated tumor glycolytic reprogramming | Nature Communications
Description:
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. PFKFB3 enhances glycolysis to promote cancer cell proliferation. Here, the authors identify a long noncoding RNA in esophageal squamous cell carcinoma, AGPG, which interacts with PFKFB3 and promotes its stability, leading to increased glycolysis and proliferation.
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Keywords {π}
agpg, pfkfb, cell, fig, cells, expression, pubmed, cancer, article, escc, analysis, google, scholar, supplementary, cas, rna, assays, data, proliferation, performed, glycolysis, levels, kyse, nature, tumor, metabolism, central, china, tissues, knockdown, qpcr, showed, lncrnas, ubiquitination, cycle, abcam, binding, detection, test, sysucc, western, study, usa, high, glucose, significantly, independent, crispr, role, interaction,
Topics {βοΈ}
plv-u6-agpg rna sgrna01-7sk-sgrna02-efs-hcas9-2a-puro rui-hua xuΒ &Β huai-qiang ju nature portfolio crispr/cas9 genome-editing system open-access database privacy policy fundamental research funds rui-hua xu advertising preventing apc/c-mediated ubiquitination anaphase-promoting complex apc/c21 apc/c-mediated cellular ubiquitylation huai-qiang ju degradation involving apc/c-cdh1 flag-tagged pfkfb3 wild-type p53-agpg-pfkfb3 axis leads research design sun yat-sen university reprints apc/c-mediated ubiquitination japan nature 493 nature 379 nature 509 nature 541 nature crispr/cas9-based strategy50 research small cell carcinoma robust transcriptome-wide discovery rna interference-based strategies thermo fisher scientific social media agpg-mediated cell proliferation p53-agpg-pfkfb3 axis cdna libraries ikk-nf-kappab pathway sirna library targeting amp-activated protein kinase vivo protein-rna interactions pcr primer acactaggccatgcaccaa/gcccacaggccaaattcattc k-rasg12v transformation leads vivo-optimized agpg inhibitor p53-mediated cellular response mcp-3flag plasmids led 13c-labeled metabolic intermediates flag-tagged pfkfb3 wt antibody-coated sepharose beads pcr primer gcaacaccacgaatcccaac/ttgtcccgctctggaaactc hypoxia-induced cisplatin resistance
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headline:Long noncoding RNA AGPG regulates PFKFB3-mediated tumor glycolytic reprogramming
description: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. PFKFB3 enhances glycolysis to promote cancer cell proliferation. Here, the authors identify a long noncoding RNA in esophageal squamous cell carcinoma, AGPG, which interacts with PFKFB3 and promotes its stability, leading to increased glycolysis and proliferation.
datePublished:2020-03-20T00:00:00Z
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headline:Long noncoding RNA AGPG regulates PFKFB3-mediated tumor glycolytic reprogramming
description: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. PFKFB3 enhances glycolysis to promote cancer cell proliferation. Here, the authors identify a long noncoding RNA in esophageal squamous cell carcinoma, AGPG, which interacts with PFKFB3 and promotes its stability, leading to increased glycolysis and proliferation.
datePublished:2020-03-20T00:00:00Z
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Cancer metabolism
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multidisciplinary
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