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circ-NRIP1 Promotes Glycolysis and Tumor Progression by Regulating miR-186-5p/MYH9 Axis in Gastric Cancer

Authors Liu Y, Jiang Y, Xu L, Qu C, Zhang L, Xiao X, Chen W, Li K, Liang Q, Wu H

Received 14 January 2020

Accepted for publication 22 May 2020

Published 17 July 2020 Volume 2020:12 Pages 5945—5956

DOI https://doi.org/10.2147/CMAR.S245941

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Chien-Feng Li


Yanhong Liu, Yuanyuan Jiang, Lidong Xu, Chongxing Qu, Lei Zhang, Xingguo Xiao, Wenxia Chen, Kunkun Li, Qianping Liang, Huili Wu

Department of Gastroenterology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, People’s Republic of China

Correspondence: Huili Wu
Department of Gastroenterology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, No. 124, Funiu Road, Zhongyuan District, Zhengzhou City, Henan Province 450007, People’s Republic of China
Tel +86-0371-67690972
Email wuhuili00965@163.com

Background: Gastric cancer (GC) is a severe threat to human life, with high incidence and mortality. Circular RNAs (circRNAs) play crucial roles in the progression of GC. This study attempted to investigate the potential role of circ-NRIP1 and associated action mechanisms in GC cells.
Methods: The expression of circ-NRIP1 and miR-186-5p was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability, apoptosis, and migration were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, flow cytometry assay, and transwell assay, respectively. Cellular glycolysis, including cellular glucose uptake, lactate, and ATP/ADP ratios, was also detected by commercial assay kits. The protein levels of hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2) were quantified by Western blot. The relationship between miR-186-5p and circ-NRIP1 or myosin heavy chain 9 (MYH9) was predicted by the online bioinformatics tool, starBase, and verified by dual-luciferase reporter assay. Xenograft tumor model was used to evaluate biological function in vivo.
Results: The expression of circ-NRIP1 was up-regulated in tissues of GC patients and cells, as well as negatively associated with that of miR-186-5p in tissues. circ-NRIP1 knockdown inhibited cell proliferation, migration, and glycolysis, but induced apoptosis in HGC-27 and AGS cells. circ-NRIP1 competitively targeted miR-186-5p, and MYH9 was a target of miR-186-5p. miR-186-5p knockdown inverted the bio-function effects and glycolytic activation from circ-NRIP1 silencing in HGC-27 and AGS cells. Meanwhile, MYH9 overexpression could rescue the effects of miR-186-5p. Besides, miR-186-5p knockdown inverted the expression pattern of si-circ-NRIP1 transfection in GC cells. Additionally, in vivo experiments confirmed that sh-circ-NRIP1 inhibited tumor growth.
Conclusion: circ-NRIP1 accelerated the glycolysis and GC progression by modulating MYH9 via miR-186-5p, suggesting that circ-NRIP1 was a promising biomarker for the treatment of GC.

Keywords: GC, circ-NRIP1, miR-186-5p, glycolysis, MYH9

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