Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2019; 25(35): 5310-5322
Published online Sep 21, 2019. doi: 10.3748/wjg.v25.i35.5310
LncRNA-ATB promotes autophagy by activating Yes-associated protein and inducing autophagy-related protein 5 expression in hepatocellular carcinoma
Chuan-Zhuo Wang, Guang-Xin Yan, De-Shuo Dong, He Xin, Zhao-Yu Liu
Chuan-Zhuo Wang, Guang-Xin Yan, De-Shuo Dong, He Xin, Zhao-Yu Liu, Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
Author contributions: Wang CZ and Liu ZY conceived the study and participated in its design; Wang CZ, Yan GX, and Dong DS performed the experiments; Xin H performed the statistical analysis.
Institutional review board statement: The human subject research performed in this study was approved by the Clinical Research Ethics Committee of the Hospital of China Medical University.
Conflict-of-interest statement: The authors declare no conflicts of interest regarding the publication of this paper.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Zhao-Yu Liu, MD, Academic Research, Professor, Chairman, Department of Radiology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang 110004, Liaoning Province, China. liuzy@sj-hospital.org
Telephone: +86-18940251226 Fax: +86-24-23901480
Received: May 24, 2019
Peer-review started: May 27, 2019
First decision: July 21, 2019
Revised: July 30, 2019
Accepted: August 7, 2019
Article in press: August 7, 2019
Published online: September 21, 2019
Processing time: 122 Days and 2.5 Hours
Abstract
BACKGROUND

Long non-coding RNAs (lncRNAs) play important roles in many diseases, including hepatocellular carcinoma (HCC). Autophagy is a metabolic pathway that facilitates cancer cell survival in response to stress. The relationship between autophagy and the lncRNA-activated by transforming growth factor beta (lncRNA-ATB) in HCC remains unknown.

AIM

To explore the influence of lncRNA-ATB in regulating autophagy in HCC cells and the underlying mechanism.

METHODS

In the present study, we evaluated lncRNA-ATB expression in tumor and adjacent non-tumor tissues from 72 HCC cases by real-time PCR. We evaluated the role of lncRNA-ATB in the proliferation and clonogenicity of HCC cells in vitro. The effect of lncRNA-ATB on autophagy was determined using a LC3-GFP reporter and transmission electron microscopy. Furthermore, the mechanism by which lncRNA-ATB regulates autophagy was explored by immunofluorescence staining, RNA immunoprecipitation (RIP), and Western blot.

RESULTS

The expression of lncRNA-ATB was higher in HCC tissues than in normal liver tissues, and lncRNA-ATB expression was positively correlated with tumor size, TNM stage, and poorer survival of patients with HCC. Moreover, ectopic overexpression of lncRNA-ATB promoted cell proliferation and clonogenicnity of HCC cells in vitro. LncRNA-ATB promoted autophagy by activating Yes-associated protein (YAP). Moreover, lncRNA-ATB interacted with autophagy-related protein 5 (ATG5) mRNA and increased ATG5 expression.

CONCLUSION

LncRNA-ATB regulates autophagy by activating YAP and increasing ATG5 expression. Our data demonstrate a novel function for lncRNA-ATB in autophagy and suggest that lncRNA-ATB plays an important role in HCC.

Keywords: LncRNA-ATB; Autophagy; Yes-associated protein; Autophagy-related protein 5; Hepatocellular carcinoma

Core tip: In the present study, we identified the relationship between lncRNA-activated by transforming growth factor beta (lncRNA-ATB) and autophagy in hepatocellular carcinoma (HCC). We demonstrated that lncRNA-ATB promoted autophagic flux in HCC cells. We found that lncRNA-ATB regulated autophagy by activating Yes-associated protein and increasing autophagy-related protein 5 expression. Our findings provide a novel link between lncRNA-ATB and autophagy, and suggest that lncRNA-ATB may be a potential therapeutic target in the treatment of HCC.