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Metformin Activates the AMPK-mTOR Pathway by Modulating lncRNA TUG1乐动体育西班牙人 to Induce Autophagy and Inhibit Atherosclerosis

Authors You G, Long X, , Huang J, Tian M, Xiao Y, Deng S, Wu Q

Received 10 October 2019

Accepted for publication乐动体育西班牙人 11 January 2020

Published 3 February 2020 Volume 2020:14 Pages 457—468

DOI乐动体育西班牙人

Checked for plagiarism Yes

Review by Single-blind乐动体育西班牙人

Peer reviewer comments 2

Editor who approved publication: Dr Georgios D. Panos乐动体育西班牙人


Ganhua You, 1, 2 Xiangshu Long, 3, 4 Fang Song, 3, 4 Jing Huang, 3, 4 Maobo Tian, 3, 4 Yan Xiao, 3, 4 Shiyan Deng, 3, 4 Qiang Wu 3, 4

1Guizhou University School of Medicine, Guiyang 550025, People’s Republic of China; 2Guizhou Institute for Food and Drug Control, Guiyang 550004, People’s Republic of China; 3Department of Cardiology, Guizhou Provincial People’s Hospital, Guiyang 550002, People’s Republic of China; 4Department of Cardiology, People’s Hospital of Guizhou University, Guiyang 550002, People’s Republic of China

Correspondence: Qiang Wu
Department of Cardiology, Guizhou Provincial People’s Hospital, 83 Zhongshan East Road, Guiyang, Guizhou, People’s Republic of China
Tel +86-0851-85937194
Fax +86-0851-85924943
Email wqgz0851@126.com

Background: Metformin has been shown to inhibit the proliferation and migration of vascular wall cells. However, the mechanism through which metformin acts on atherosclerosis (AS) via the long non-coding RNA taurine up-regulated gene 1 (lncRNA TUG1) is still unknown. Thus, this research investigated the effect of metformin and lncRNA TUG1 on AS.
Methods: First, qRT-PCR was used to detect the expression of lncRNA TUG1 in patients with coronary heart disease (CHD). Then, the correlation between metformin and TUG1 expression in vitro and their effects on proliferation, migration, and autophagy in vascular wall cells were examined. Furthermore, in vivo experiments were performed to verify the anti-AS effect of metformin and TUG1 to provide a new strategy for the prevention and treatment of AS.
Results: qRT-PCR results suggested that lncRNA TUG1 expression was robustly upregulated in patients with CHD. In vitro experiments indicated that after metformin administration, the expression of lncRNA TUG1 decreased in a time-dependent manner. Metformin and TUG1 knockdown via small interfering RNA both inhibited proliferation and migration while promoted autophagy via the AMPK/mTOR pathway in vascular wall cells. In vivo experiments with a rat AS model further demonstrated that metformin and sh-TUG1 could inhibit the progression of AS.
Conclusion: Taken together, our data demonstrate that metformin might function to prevent AS by activating the AMPK/mTOR pathway via lncRNA TUG1.

Keywords: metformin, taurine up-regulated gene 1, AMPK/mTOR, autophagy, atherosclerosis

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