lncRNA GAS6-AS1 inhibits progression and glucose metabolism reprogramming in LUAD via repressing E2F1-mediated transcription of GLUT1

Glucose metabolism reprogramming is one of the hallmarks of cancer cells, although functional and regulatory mechanisms of long noncoding RNA (lncRNA) in the contribution of glucose metabolism in lung adenocarcinoma (LUAD) remain incompletely understood. The aim of this study was to uncover the role...

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Main Authors: Jing Luo, Huishan Wang, Li Wang, Gaoming Wang, Yu Yao, Kai Xie, Xiaokun Li, Lin Xu, Yi Shen, Binhui Ren
Format: Article
Language:English
Published: Elsevier 2021-09-01
Series:Molecular Therapy: Nucleic Acids
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Online Access:http://www.sciencedirect.com/science/article/pii/S2162253121001165
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author Jing Luo
Huishan Wang
Li Wang
Gaoming Wang
Yu Yao
Kai Xie
Xiaokun Li
Lin Xu
Yi Shen
Binhui Ren
author_facet Jing Luo
Huishan Wang
Li Wang
Gaoming Wang
Yu Yao
Kai Xie
Xiaokun Li
Lin Xu
Yi Shen
Binhui Ren
author_sort Jing Luo
collection DOAJ
description Glucose metabolism reprogramming is one of the hallmarks of cancer cells, although functional and regulatory mechanisms of long noncoding RNA (lncRNA) in the contribution of glucose metabolism in lung adenocarcinoma (LUAD) remain incompletely understood. The aim of this study was to uncover the role of GAS6-AS1 in the regulation of progression and glucose metabolism in LUAD. We discovered that overexpression of GAS6-AS1 suppressed tumor progression of LUAD both in vitro and in vivo. Metabolism-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. 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 may serve as a prognostic marker and therapeutic target in LUAD.
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spelling doaj.art-08879b54ab884ff0b96b748c768df37d2022-12-21T20:00:53ZengElsevierMolecular Therapy: Nucleic Acids2162-25312021-09-01251124lncRNA GAS6-AS1 inhibits progression and glucose metabolism reprogramming in LUAD via repressing E2F1-mediated transcription of GLUT1Jing Luo0Huishan Wang1Li Wang2Gaoming Wang3Yu Yao4Kai Xie5Xiaokun Li6Lin Xu7Yi Shen8Binhui Ren9Department of Thoracic Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing 210000, China; Department of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210000, ChinaDepartment of Gastroenterology, Shanghai Songjiang District Central Hospital, Shanghai 200000, ChinaDepartment of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, ChinaDepartment of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210000, China; Department of Thoracic Surgery, Xuzhou Central Hospital, Xuzhou 221000, ChinaDepartment of Respiratory Medicine, Nanjing Second Hospital, Nanjing 210000, ChinaDepartment of Thoracic Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing 210000, China; Department of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210000, ChinaDepartment of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210000, ChinaDepartment of Thoracic Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing 210000, China; Corresponding author: Lin Xu, MD, Department of Thoracic Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing 210000, China.Department of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210000, China; Corresponding author: Yi Shen, MD, Department of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210000, China.Department of Thoracic Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing 210000, China; Corresponding author: Binhui Ren, MD, Department of Thoracic Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing 210000, China.Glucose metabolism reprogramming is one of the hallmarks of cancer cells, although functional and regulatory mechanisms of long noncoding RNA (lncRNA) in the contribution of glucose metabolism in lung adenocarcinoma (LUAD) remain incompletely understood. The aim of this study was to uncover the role of GAS6-AS1 in the regulation of progression and glucose metabolism in LUAD. We discovered that overexpression of GAS6-AS1 suppressed tumor progression of LUAD both in vitro and in vivo. Metabolism-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. 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 may serve as a prognostic marker and therapeutic target in LUAD.http://www.sciencedirect.com/science/article/pii/S2162253121001165GAS6-AS1lung adenocarcinomaglucose metabolismE2F1GLUT1
spellingShingle Jing Luo
Huishan Wang
Li Wang
Gaoming Wang
Yu Yao
Kai Xie
Xiaokun Li
Lin Xu
Yi Shen
Binhui Ren
lncRNA GAS6-AS1 inhibits progression and glucose metabolism reprogramming in LUAD via repressing E2F1-mediated transcription of GLUT1
Molecular Therapy: Nucleic Acids
GAS6-AS1
lung adenocarcinoma
glucose metabolism
E2F1
GLUT1
title lncRNA GAS6-AS1 inhibits progression and glucose metabolism reprogramming in LUAD via repressing E2F1-mediated transcription of GLUT1
title_full lncRNA GAS6-AS1 inhibits progression and glucose metabolism reprogramming in LUAD via repressing E2F1-mediated transcription of GLUT1
title_fullStr lncRNA GAS6-AS1 inhibits progression and glucose metabolism reprogramming in LUAD via repressing E2F1-mediated transcription of GLUT1
title_full_unstemmed lncRNA GAS6-AS1 inhibits progression and glucose metabolism reprogramming in LUAD via repressing E2F1-mediated transcription of GLUT1
title_short lncRNA GAS6-AS1 inhibits progression and glucose metabolism reprogramming in LUAD via repressing E2F1-mediated transcription of GLUT1
title_sort lncrna gas6 as1 inhibits progression and glucose metabolism reprogramming in luad via repressing e2f1 mediated transcription of glut1
topic GAS6-AS1
lung adenocarcinoma
glucose metabolism
E2F1
GLUT1
url http://www.sciencedirect.com/science/article/pii/S2162253121001165
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