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NR2F1-AS1/miR-140/HK2 Axis Regulates Hypoxia-Induced Glycolysis and Migration in Hepatocellular Carcinoma

Authors Li X, Li Y, Bai S, Zhang J, Liu Z, Yang J

Received 8 June 2020

Accepted for publication 9 September 2020

Published 15 January 2021 Volume 2021:13 Pages 427—437

DOI https://doi.org/10.2147/CMAR.S266797

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Seema Singh


Xiao Li,1 Yize Li,2 Shuang Bai,2 Jing Zhang,2 Zhengcai Liu,1 Jingyue Yang2

1Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xian 710032, People’s Republic of China; 2Department of Clinical Oncology, Xijing Hospital, Fourth Military Medical University, Xian 710032, People’s Republic of China

Correspondence: Jingyue Yang
Department of Clinical Oncology, Xijing Hospital, Fourth Military Medical University, 17 Chonglexi Road, Xian, Shaanxi Province 710032, People’s Republic of China
Tel +86-02984775412
Email yjyue2000@163.com

Background: Hypoxia is an important feature for the progression of hepatocellular carcinoma (HCC). Long noncoding RNA nuclear receptor subfamily 2 group F member 1 antisense RNA 1 (NR2F1-AS1) is dysregulated in HCC. However, the role and mechanism of N2RF1-AS1 in hypoxia-induced glycolysis and migration remain unclear.
Materials and Methods: Tumor tissues and adjacent samples were harvested from 40 HCC patients. HCC cells were treated by hypoxia. The levels of NR2F1-AS1, microRNA (miR)-140, and hexokinase 2 (HK2) were examined via quantitative reverse transcription polymerase chain reaction or Western blot. Glycolysis was analyzed via glucose uptake, lactate production, and adenosine triphosphate (ATP) levels. Cell migration was analyzed via transwell assay. The target association was analyzed via dual-luciferase reporter assay and RNA immunoprecipitation.
Results: NR2F1-AS1 level was enhanced in HCC tissues and cells. High expression of NR2F1-AS1 indicated poor overall survival. Silence of NR2F1-AS1 repressed hypoxia-induced glycolysis and migration in HCC cells. NR2F1-AS1 could regulate HK2 expression by modulating miR-140. miR-140 down-regulation or HK2 up-regulation mitigated the influence of NR2F1-AS1 silence on hypoxia-induced glycolysis and migration in HCC cells.
Conclusion: NR2F1-AS1 knockdown restrained hypoxia-induced glycolysis and migration in HCC cells via increasing miR-140 and decreasing HK2.

Keywords: hepatocellular carcinoma, NR2F1-AS1, miR-140, HK2, glycolysis, migration

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