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

Li,Xiao; Zhao,Qi; Qi,Jianni; Wang,Wenwen; Zhang,Di; Li,Zhen; Qin,Chengyong

doi:10.3892/ijo.2018.4418

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

Authors:
- Xiao Li
- Qi Zhao
- Jianni Qi
- Wenwen Wang
- Di Zhang
- Zhen Li
- Chengyong Qin
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Affiliations: Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Shandong Provincial Engineering and Technological Research Center for Liver Diseases Prevention and Control, Jinan, Shandong 250021, P.R. China
Published online on: May 23, 2018 https://doi.org/10.3892/ijo.2018.4418
Pages: 551-566
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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