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10.1186/s12885-017-3473-4

http://scihub22266oqcxt.onion/10.1186/s12885-017-3473-4
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suck abstract from ncbi


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pmid28693517
      BMC+Cancer 2017 ; 17 (1 ): 477
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  • JMJD2A promotes the Warburg effect and nasopharyngeal carcinoma progression by transactivating LDHA expression #MMPMID28693517
  • Su Y ; Yu QH ; Wang XY ; Yu LP ; Wang ZF ; Cao YC ; Li JD
  • BMC Cancer 2017[Jul]; 17 (1 ): 477 PMID28693517 show ga
  • BACKGROUND: Jumonji C domain 2A (JMJD2A), as a histone demethylases, plays a vital role in tumorigenesis and progression. But, its functions and underlying mechanisms of JMJD2A in nasopharyngeal carcinoma (NPC) metabolism are remained to be clarified. In this study, we investigated glycolysis regulation by JMJD2A in NPC and the possible mechanism. METHODS: JMJD2A expression was detected by Western blotting and Reverse transcription quantitative real-time PCR analysis. Then, we knocked down and ectopically expressed JMJD2A to detect changes in glycolytic enzymes. We also evaluated the impacts of JMJD2A-lactate dehydrogenase A (LDHA) signaling on NPC cell proliferation, migration and invasion. ChIP assays were used to test whether JMJD2A bound to the LDHA promoter. Finally, IHC was used to verify JMJD2A and LDHA expression in NPC tissue samples and analyze their correlation between expression and clinical features. RESULTS: JMJD2A was expressed at high levels in NPC tumor tissues and cell lines. Both JMJD2A and LDHA expression were positively correlated with the tumor stage, metastasis and clinical stage. Additionally, the level of JMJD2A was positively correlated with LDHA expression in NPC patients, and higher JMJD2A and LDHA expression predicted a worse prognosis. JMJD2A alteration did not influence most of glycolytic enzymes expression, with the exception of PFK-L, PGAM-1, LDHB and LDHA, and LDHA exhibited the greatest decrease in expression. JMJD2A silencing decreased LDHA expression and the intracellular ATP level and increased LDH activity, lactate production and glucose utilization, while JMJD2A overexpression produced the opposite results. Furthermore, JMJD2A could combine to LDHA promoter region and regulate LDHA expression at the level of transcription. Activated JMJD2A-LDHA signaling pathway promoted NPC cell proliferation, migration and invasion. CONCLUSIONS: JMJD2A regulated aerobic glycolysis by regulating LDHA expression. Therefore, the novel JMJD2A-LDHA signaling pathway could contribute to the Warburg effects in NPC progression.
  • |*Gene Expression Regulation, Neoplastic [MESH]
  • |Adenosine Triphosphate/metabolism [MESH]
  • |Adult [MESH]
  • |Aged [MESH]
  • |Biomarkers [MESH]
  • |Carcinoma/*genetics/*metabolism/mortality/pathology [MESH]
  • |Cell Line, Tumor [MESH]
  • |Cell Movement/genetics [MESH]
  • |Cell Proliferation [MESH]
  • |Disease Progression [MESH]
  • |Enzyme Activation [MESH]
  • |Female [MESH]
  • |Gene Expression [MESH]
  • |Genes, Reporter [MESH]
  • |Glucose/metabolism [MESH]
  • |Glycolysis [MESH]
  • |Humans [MESH]
  • |Isoenzymes/genetics/metabolism [MESH]
  • |Jumonji Domain-Containing Histone Demethylases/*metabolism [MESH]
  • |Kaplan-Meier Estimate [MESH]
  • |L-Lactate Dehydrogenase/*genetics/metabolism [MESH]
  • |Lactate Dehydrogenase 5 [MESH]
  • |Lactic Acid/metabolism [MESH]
  • |Male [MESH]
  • |Middle Aged [MESH]
  • |Nasopharyngeal Carcinoma [MESH]
  • |Nasopharyngeal Neoplasms/*genetics/*metabolism/mortality/pathology [MESH]
  • |Neoplasm Grading [MESH]
  • |Neoplasm Staging [MESH]
  • |Signal Transduction [MESH]


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