Observational Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 21, 2019; 25(15): 1890-1898
Published online Apr 21, 2019. doi: 10.3748/wjg.v25.i15.1890
Mechanism of exosomal microRNA-224 in development of hepatocellular carcinoma and its diagnostic and prognostic value
Yao Cui, Hai-Feng Xu, Ming-Yue Liu, Yu-Jie Xu, Jun-Chuang He, Yun Zhou, Shun-Dong Cang
Yao Cui, Ming-Yue Liu, Yu-Jie Xu, Yun Zhou, Shun-Dong Cang, Department of Oncology, Henan Key Laboratory for Precision Medicine in Cancer, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou 450003, Henan Province, China
Hai-Feng Xu, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Interventional Therapy Department, Peking University Cancer Hospital and Institute, Beijing 100142, China
Jun-Chuang He, Department of Hepatobiliary Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou 450003, Henan Province, China
Author contributions: Cui Y, Xu HF, and Cang SD designed the study; Cui Y, Xu HF, Liu MY, and Xu YJ performed the research; Cui Y, He JC, and Cang SD analyzed the data; Cui Y and Xu HF wrote the paper; Cang SD revised the manuscript for final submission; Cui Y and Xu HF contributed equally to this study.
Supported by the Scientific and Technological Research Project of Henan Province, No. 162102310024.
Institutional review board statement: The study was reviewed and approved by the Peking University Cancer Hospital and Institute review board.
Informed consent statement: All study participants or their legal guardian provided written informed consent prior to study enrollment.
Conflict-of-interest statement: We declare that we have no financial or personal relationships with other individuals or organizations that can inappropriately influence our work and that there is no professional or other personal interest of any nature in any product, service and/or company that could be construed as influencing the position presented in or the review of the manuscript.
Data sharing statement: No additional data are available
STROBE statement: The manuscript was prepared according to the STROBE Checklist.
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: Shun-Dong Cang, MD, Associate Professor, Doctor, Department of Oncology, Henan Key Laboratory for Precision Medicine in cancer, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, No. 7, Weiwu Road, Zhengzhou 450003, Henan Province, China. cangshundonghn@126.com
Telephone: +86-371-65580092 Fax: +86-371-65580092
Received: December 27, 2018
Peer-review started: December 27, 2018
First decision: January 18, 2019
Revised: February 17, 2019
Accepted: February 22, 2019
Article in press: February 23, 2019
Published online: April 21, 2019
Processing time: 112 Days and 21.1 Hours
Abstract
BACKGROUND

Exosomes contain proteins, lipids, and biological molecules such as DNA and RNA. Nucleic acids in exosomes are a group of molecules that can act as biomarkers. Currently, there are many reports on exosomal microRNAs, which are ideal biomarkers for the early diagnosis of cancer. However, there are few reports on the role of exosomal microRNAs in the diagnosis and prognosis of hepatocellular carcinoma (HCC).

AIM

To understand the mechanism of exosomal microRNA-224 (miR-224) in the development of HCC and evaluate its diagnostic and prognostic value.

METHODS

Cell culture and transfection of exosomal miRNA-224, real-time quantitative PCR, luciferase reporter assay, and other methods were used to find new biomarkers related to the development of HCC that can be used to diagnose HCC and predict HCC prognosis.

RESULTS

By targeting glycine N-methyltransferase, incubating exosomes with miR-224 mimic resulted in a significant increase in cell proliferation compared to that of the control group, while incubation with the miR-224 inhibitor significantly reduced cell proliferation. The same results were obtained for the cell invasion assay. Serum exosomal miR-224 did have some ability to differentiate patients with HCC from healthy controls, with an area under the curve of 0.910, and HCC patients with higher serum exosomal miR-224 expression had lower overall survival.

CONCLUSION

Exosomal miR-224 is a tumor promotor and can be a marker of diagnosis and prognosis of HCC patients, however, its ability to distinguish liver diseases needs further verification.

Keywords: Hepatocellular carcinoma; Serum; Exosome; MicroRNA-224; Biomarker

Core tip: We aimed to understand the mechanism of exosomal microRNA-224 (miR-224) in the development of hepatocellular carcinoma (HCC) and to evaluate its diagnostic and prognostic value for HCC patients. By directly targeting the 3'-untranslated region of glycine N-methyltransferase, exosomal miR-224 inhibits its expression to promote proliferation and invasion. In addition, serum exosomal miR-224 also has potential diagnostic and prognostic value for HCC.