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
ARTICLE HIGHLIGHTS
Research background

Long non-coding RNAs (lncRNAs) play a vital role in the progression of hepatocellular carcinoma (HCC). Autophagy is a dynamic metabolic process that supports 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.

Research motivation

A large number of aberrantly expressed genes influence the progression of HCC, but the molecular mechanisms governing HCC malignancy are still not entirely clear, and the potential connection between lncRNAs and autophagy remains to be fully elucidated. There is an important and unmet need to elucidate the molecular mechanisms of autophagy, and to capitalize on that knowledge to develop autophagy-related methods as therapeutic strategies for treatment of HCC.

Research objectives

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

Research methods

We compared the expression of lncRNA-ATB in 72 HCC tissues and adjacent non-tumor tissues by real-time PCR. The role of lncRNA-ATB in cell proliferation and colony formation was evaluated 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, and Western blot.

Research results

We found that lncRNA-ATB was up-regulated in HCC and lncRNA-ATB expression positively correlated with tumor size, TNM stage, and poor survival of HCC patients. Overexpression of lncRNA-ATB promoted cell proliferation and colony formation 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.

Research conclusions

Our study reveals that lncRNA-ATB regulates autophagy by activating YAP and increasing ATG5 expression. These results provide new insights into the role of lncRNA-ATB in autophagy in HCC.

Research perspectives

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.