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论文题目: The microRNA-182-PDK4 axis regulates lung tumorigenesis by modulating pyruvate dehydrogenase and lipogenesis
英文论文题目: The microRNA-182-PDK4 axis regulates lung tumorigenesis by modulating pyruvate dehydrogenase and lipogenesis
第一作者: Li, G; Li, M; Hu, J; Lei, R; Xiong, H; Ji, H; Yin, H; Wei, Q; Hu, G
英文第一作者: Li, G; Li, M; Hu, J; Lei, R; Xiong, H; Ji, H; Yin, H; Wei, Q; Hu, G
联系作者: Hu, G (reprint author), Chinese Acad Sci, Key Lab Stem Cell Biol, Inst Hlth Sci, Shanghai Inst Biol Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
英文联系作者: Hu, G (reprint author), Chinese Acad Sci, Key Lab Stem Cell Biol, Inst Hlth Sci, Shanghai Inst Biol Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
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发表年度: 2017
卷: 36
期: 7
页码: 989-998
摘要: Reprogrammed metabolism is one of the hallmarks of cancer. The dysregulation of glycolysis in cancer has been heavily studied. However, it remains largely unclear how other metabolic processes are regulated in cancer cells. Here we show that microRNA-182 (miR-182) suppresses pyruvate dehydrogenase (PDH) kinase 4 (PDK4) and promotes lung tumorigenesis. miR-182 is dysregulated and inversely correlated with PDK4 in human lung adenocarcinomas. The miR-182-PDK4 axis regulates lung cancer cell growth by modulating the activity of PDH, the gatekeeping enzyme of pyruvate flux into acetyl-CoA, and subsequently de novo lipogenesis of cancer cells. Suppression of lipogenesis by silencing ATP citrate lyase (ACLY) and fatty acid synthase (FASN) or by chemical inhibitors diminishes the effects of miR-182-PDK4 in tumor growth. Alteration of de novo lipogenesis also affects reactive oxygen species (ROS) production and the downstream JNK signaling pathway. Hence, our work suggests that the miR-182-PDK4 axis is a crucial regulator of cancer cell metabolism and a potential target for antitumor therapy.
英文摘要: Reprogrammed metabolism is one of the hallmarks of cancer. The dysregulation of glycolysis in cancer has been heavily studied. However, it remains largely unclear how other metabolic processes are regulated in cancer cells. Here we show that microRNA-182 (miR-182) suppresses pyruvate dehydrogenase (PDH) kinase 4 (PDK4) and promotes lung tumorigenesis. miR-182 is dysregulated and inversely correlated with PDK4 in human lung adenocarcinomas. The miR-182-PDK4 axis regulates lung cancer cell growth by modulating the activity of PDH, the gatekeeping enzyme of pyruvate flux into acetyl-CoA, and subsequently de novo lipogenesis of cancer cells. Suppression of lipogenesis by silencing ATP citrate lyase (ACLY) and fatty acid synthase (FASN) or by chemical inhibitors diminishes the effects of miR-182-PDK4 in tumor growth. Alteration of de novo lipogenesis also affects reactive oxygen species (ROS) production and the downstream JNK signaling pathway. Hence, our work suggests that the miR-182-PDK4 axis is a crucial regulator of cancer cell metabolism and a potential target for antitumor therapy.
刊物名称: ONCOGENE
英文刊物名称: ONCOGENE
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学科: Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity
英文学科: Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity
影响因子: 7.519
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论文类别: Article
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