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Research
Long Noncoding RNA GAS6-AS1 Inhibits Progression and Glucose Metabolism Reprogramming in Lung Adenocarcinoma Via Repressing E2F1-Mediated Transcription of GLUT1
Lin Xu
Jiangsu Cancer Hospital
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Glucose metabolism reprogramming is one of the hallmarks of cancer cells. While functional and regulatory mechanism of long noncoding RNA (lncRNA) in the contribution of glucose metabolism in lung adenocarcinoma (LUAD) remains incompletely understood. The aim of this study was to uncover the roles for GAS6-AS1 in the regulation of progression and glucose metabolism in LUAD.
Methods
The tumor-suppressive function of GAS6-AS1 was determined by experiments in vitro and nude mice xenograft models. The role of GAS6-AS1 in regulating cancer glucose metabolism was proved by detecting glucose uptake, lactate production, pyruvate production and extracellular acidification rate (ECAR). RNA pull-down assay, RNA immunoprecipitation (RIP) assay, luciferase reporter assay and Chromatin Immunoprecipitation (ChIP) assay were used to identify the underlying molecular mechanisms of GAS6-AS1. And the expression level of GAS6-AS1 in LUAD tissues and cells was measured by quantitative real-time PCR.
Results
Overexpression of GAS6-AS1 suppressed tumor progression of LUAD both in vitro and in vivo. Metabolic-related assays revealed that GAS6-AS1 inhibited glucose metabolism reprogramming. Mechanically, GAS6-AS1 was found to repress the expression of glucose transporter GLUT1, a key regulator of glucose metabolism. Ectopic expression of GLUT1 restored the inhibition effect of GAS6-AS1 on cancer progression and glucose metabolism reprogramming. Further investigation identified that GAS6-AS1 directly interacted with transcription factor E2F1 and suppressed E2F1-mediated transcription of GLUT1. And GAS6-AS1 was downregulated in LUAD tissues and correlated with clinicopathological characteristics and survival of patients.
Conclusions
Taken together, our results identified GAS6-AS1 as a novel tumor suppressor in LUAD and unraveled its underlying molecular mechanism in reprogramming glucose metabolism. GAS6-AS1 potentially served as a prognostic marker and therapeutic target in LUAD.
Keywords
GAS6-AS1, lung adenocarcinoma, glucose metabolism, E2F1, GLUT1
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This is a preprint. It has not completed peer review.
Research
Long Noncoding RNA GAS6-AS1 Inhibits Progression and Glucose Metabolism Reprogramming in Lung Adenocarcinoma Via Repressing E2F1-Mediated Transcription of GLUT1
Lin Xu
Jiangsu Cancer Hospital
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 23 Sep, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cancer Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Glucose metabolism reprogramming is one of the hallmarks of cancer cells. While functional and regulatory mechanism of long noncoding RNA (lncRNA) in the contribution of glucose metabolism in lung adenocarcinoma (LUAD) remains incompletely understood. The aim of this study was to uncover the roles for GAS6-AS1 in the regulation of progression and glucose metabolism in LUAD.
Methods
The tumor-suppressive function of GAS6-AS1 was determined by experiments in vitro and nude mice xenograft models. The role of GAS6-AS1 in regulating cancer glucose metabolism was proved by detecting glucose uptake, lactate production, pyruvate production and extracellular acidification rate (ECAR). RNA pull-down assay, RNA immunoprecipitation (RIP) assay, luciferase reporter assay and Chromatin Immunoprecipitation (ChIP) assay were used to identify the underlying molecular mechanisms of GAS6-AS1. And the expression level of GAS6-AS1 in LUAD tissues and cells was measured by quantitative real-time PCR.
Results
Overexpression of GAS6-AS1 suppressed tumor progression of LUAD both in vitro and in vivo. Metabolic-related assays revealed that GAS6-AS1 inhibited glucose metabolism reprogramming. Mechanically, GAS6-AS1 was found to repress the expression of glucose transporter GLUT1, a key regulator of glucose metabolism. Ectopic expression of GLUT1 restored the inhibition effect of GAS6-AS1 on cancer progression and glucose metabolism reprogramming. Further investigation identified that GAS6-AS1 directly interacted with transcription factor E2F1 and suppressed E2F1-mediated transcription of GLUT1. And GAS6-AS1 was downregulated in LUAD tissues and correlated with clinicopathological characteristics and survival of patients.
Conclusions
Taken together, our results identified GAS6-AS1 as a novel tumor suppressor in LUAD and unraveled its underlying molecular mechanism in reprogramming glucose metabolism. GAS6-AS1 potentially served as a prognostic marker and therapeutic target in LUAD.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7