Nature communications, 2020-03, Vol.11 (1), p.1507-1507, Article 1507
2020
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- Autor(en) / Beteiligte
- Titel
- Long noncoding RNA AGPG regulates PFKFB3-mediated tumor glycolytic reprogramming
- Ist Teil von
- Nature communications, 2020-03, Vol.11 (1), p.1507-1507, Article 1507
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2020
- Quelle
- EZB-FREE-00999 freely available EZB journals
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-020-15112-3Titel-ID: cdi_doaj_primary_oai_doaj_org_article_991c7443503b477c92252788160db378
- Format
- –
- Schlagworte
- 38/1, 38/109, 38/15, 38/32, 38/35, 38/44, 38/71, 38/77, 38/88, 38/89, 6-Phosphofructo-2-kinase, 631/67, 631/67/2327, Actin, Adenomatous polyposis coli, Animals, Biomarkers, Cancer, Cell cycle, Cell growth, Cell Line, Tumor, Cell Proliferation, Cellular Reprogramming - physiology, Esophageal Squamous Cell Carcinoma - metabolism, Esophagus, Female, Fructose, Gene Knockout Techniques, Glycolysis, Humanities and Social Sciences, Humans, Kinases, Metabolism, Mice, Inbred BALB C, Mice, Nude, multidisciplinary, Mutation, p53 Protein, Phosphofructokinase-2 - metabolism, Proteasomes, Pseudogenes - genetics, Pseudogenes - physiology, Ribonucleic acid, RNA, RNA, Long Noncoding - genetics, RNA, Long Noncoding - metabolism, Science, Science (multidisciplinary), Squamous cell carcinoma, Therapeutic applications, Transcription, Tumor cells, Tumors, Ubiquitination, Up-Regulation, Xenograft Model Antitumor Assays, Xenografts, Xenotransplantation