Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2019; 25(35): 5283-5299
Published online Sep 21, 2019. doi: 10.3748/wjg.v25.i35.5283
Long non-coding RNA highly up-regulated in liver cancer promotes exosome secretion
Shun-Qi Cao, Hong Zheng, Bao-Cun Sun, Zheng-Lu Wang, Tao Liu, Dong-Hui Guo, Zhong-Yang Shen
Shun-Qi Cao, Dong-Hui Guo, Tianjin First Central Hospital Clinic Institute, Tianjin Medical University, Tianjin 300070, China
Hong Zheng, Zhong-Yang Shen, Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, China
Bao-Cun Sun, Department of Pathology, Tianjin Medical University, Tianjin 300070, China
Zheng-Lu Wang, Department of Pathology, Tianjin First Central Hospital, Tianjin 300192, China
Tao Liu, NHC Key Laboratory of Critical Care Medicine, Tianjin First Central Hospital, Tianjin 300192, China
Author contributions: Cao SQ, Zheng H, Sun BC, Wang ZL, and Liu T performed the research, analysed the data, and wrote and revised the manuscript; Shen ZY designed the study and participated in the revision of the article; all authors have read and approved the final manuscript.
Supported by Tianjin Clinical Research Center for Organ Transplantation Project, No. 15ZXLCSY00070; and The Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences, No. 2018PT32021.
Institutional review board statement: The study was reviewed and approved by the Tianjin First Central Hospital Medical Ethics Committee.
Conflict-of-interest statement: The authors declare no potential conflict of interest in this paper.
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: Zhong-Yang Shen, MD, PhD, Professor, Department of Organ Transplantation, Tianjin First Central Hospital, No. 24, Fukang Road, Nankai District, Tianjin 300192, China. shen_zhongyang@126.com
Telephone: +86-22-2362698 Fax: +86-22-2362698
Received: April 26, 2019
Peer-review started: April 26, 2019
First decision: May 24, 2019
Revised: June 7, 2019
Accepted: July 19, 2019
Article in press: May 24, 2019
Published online: September 21, 2019
Processing time: 148 Days and 22.5 Hours
ARTICLE HIGHLIGHTS
Research background

Long non-coding RNA highly up-regulated in liver cancer (lncRNA HULC) is highly expressed in hepatocellular carcinoma (HCC), and involved in the development and regulation of tumorigenesis. The relationship between HULC and exosomes has not yet been reported. Studying the mechanism of exosome secretion is helpful to reveal the pathogenesis of HCC.

Research motivation

Although HULC has long been known to play important roles in HCC, its function and regulatory mechanism are unclear. Since exosomes participate in the progression of HCC, they have been actively studied. We are interested in exploring whether HULC regulates exosome secretion and is involved in the occurrence and development of hepatocellular carcinoma. This study will provide novel insights into the mechanism of action of HULC in HCC.

Research objectives

The main objective of the study was to explore the molecular mechanism of HULC to regulate exosome secretion and and provide novel insights into the mechanism of action of HULC in HCC.

Research methods

We collected samples from serum and tissues of 30 patients with HCC. We measured HULC expression in the serum exosomes and liver cancer tissues of patients, and compared the data to those obtained from controls. We further explored the effect of HULC upregulation in HCC cell lines and studied the relationship between HULC and other RNAs using qPCR and dual-luciferase reporter assays. NTA was used to detect the quantity of exosomes.

Research results

HULC expression in serum exosomes of patients with HCC was higher than that in serum exosomes of healthy controls, and HULC levels were higher in liver cancer tissues than in adjacent tissues. The expression of HULC in serum exosomes and liver cancer tissues correlated with the tumor-node-metastasis (TNM) classification and HULC expression in tissues correlated with that in serum exosomes. HULC promoted HCC cell growth and invasion and repressed apoptosis. Additionly, it also facilitated the secretion of exosomes from HCC cells. Moreover, qPCR assays show that HULC repressed microRNA-372-3p (miR-372-3p) expression. We also identified Rab11a as a downstream target of miR-372-3p. Dual-luciferase reporter assays suggest that miR-372-3p could directly bind both HULC and Rab11a.

Research conclusions

HULC regulates Rab11a to promote secretion of exosomes by competitive miR-372-3p sharing, and this finding provides new insights into the molecular mechanism to regulate the secretion of exosomes from HCC cells.

Research perspectives

We aim to further explore the potential of serum exosome HULC as a sensitive preoperative marker for HCC and the role of HULC in the staging and prognosis evaluation of HCC.