lncRNA Ftx promotes aerobic glycolysis and tumor progression through the PPARγ pathway in hepatocellular carcinoma.

lncRNA Ftx promotes aerobic glycolysis and tumor progression through the PPARγ pathway in hepatocellular carcinoma.
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lncRNA Ftx 通过 PPARγ 途径促进肝细胞癌的有氧糖酵解和肿瘤进展

DOI:
10.3892/ijo.2018.4418
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发表时间:
2018-08
影响因子:
5.2
通讯作者:
Qin C
Qin C
中科院分区:
医学2区
文献类型:
--
作者:
Li X;Zhao Q;Qi J;Wang W;Zhang D;Li Z;Qin C

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有氧糖酵解是恶性细胞优先通过糖酵解途径代谢葡萄糖而不是氧化磷酸化以有效增殖的现象。本研究旨在探讨长链非编码RNA Ftx在肝细胞癌(HCC)有氧糖酵解和肿瘤发生中的表达及其功能意义。经鉴定,lncRNA Ftx在人HCC组织和细胞系中上调,并且显著地与侵袭性临床病理学特征相关。lncRNA Ftx过表达促进肝癌细胞的增殖、侵袭和迁移,而lncRNA Ftx敲低则产生相反的作用。此外,lncRNA Ftx影响碳水化合物代谢中关键酶的活性和表达,提示lncRNA Ftx可能参与HCC的有氧糖酵解。葡萄糖消耗、乳酸产生和葡萄糖转运蛋白表达的测量进一步支持了这一假设。从机制上讲,人HCC组织和细胞系中过氧化物酶体增殖物激活受体γ(PPARγ)的表达与lncRNA Ftx呈正相关。抑制Huh 7细胞中的PPARγ部分消除了由lncRNA Ftx诱导的葡萄糖摄取、乳酸产生和相对糖酵解酶表达的改变;类似地,Bel-7402细胞中的PPARγ激活部分挽救了lncRNA Ftx介导的改变。总之,lncRNA Ftx是瓦尔堡效应和肿瘤进展的促进剂,部分通过PPARγ途径,并且可能作为HCC治疗的有希望的治疗靶点。
Aerobic glycolysis is a phenomenon by which malignant cells preferentially metabolize glucose through the glycolytic pathway, rather than oxidative phosphorylation to proliferate efficiently. The present study aimed to investigate the expression and functional implications of long non-coding (lnc)RNA Ftx in the aerobic glycolysis and tumorigenesis of hepatocellular carcinoma (HCC). It was identified that lncRNA Ftx was upregulated in human HCC tissues and cell lines and, notably, was associated with aggressive clinicopathological features. lncRNA Ftx overexpression promoted the proliferation, invasion and migration of HCC cells, whereas lncRNA Ftx knockdown resulted in the opposite effects. Furthermore, lncRNA Ftx affected the activity and expression of key enzymes in carbohydrate metabolism, suggesting that lncRNA Ftx may be involved in aerobic glycolysis in HCC. The measurement of glucose consumption, lactate production and glucose transporter expression further supported this assumption. Mechanistically, peroxisome proliferator-activated receptor γ (PPARγ) expression in human HCC tissues and cell lines was positively correlated with lncRNA Ftx. Inhibiting PPARγ in Huh7 cells partially abrogated the alterations in glucose uptake, lactate production and relative glycolytic enzyme expression induced by lncRNA Ftx; similarly, PPARγ activation in Bel-7402 cells partially rescued the lncRNA Ftx-mediated alterations. In conclusion, lncRNA Ftx is a promoter of the Warburg effect and tumor progression, partly via the PPARγ pathway, and may serve as a promising therapeutic target for HCC treatment.
癌代谢中的葡萄糖转运蛋白。
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