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
ARTICLE HIGHLIGHTS
Research background

Hepatocellular carcinoma (HCC) is a malignant tumor with a high mortality rate. Exosomes have been shown to play an important role in tumorigenesis, cancer development, metastasis, deterioration, and immune escape.

Research motivation

We aimed to research the mechanism of exosomal microRNA-224 (miR-224) and its target in the development and invasion of HCC, and we also evaluated the diagnostic and prognostic value of miR-224 for patients with HCC.

Research methods

Cell culture and transfection of exosomal miR-224, its mimics, and its inhibitor; real-time quantitative PCR; and luciferase reporter assay were used to explore the mechanism of exosomal miR-224. HCC patients and healthy controls were used to assess the value of exosomal miR-224 in diagnosing HCC and predicting HCC prognosis.

Research results

Serum exosomes incubated with the miR-224 mimic showed a significant increase in cell proliferation and invasion when compared to the control group, while those incubated with the inhibitor showed a significant reduction. For discriminating HCC from healthy controls, serum exosomal miR-224 showed an area under the ROC curve of 0.910. Higher serum exosomal miR-224 expression levels in HCC patients were associated with lower overall survival.

Research conclusions

The results showed that exosomal miR-224 directly targets the 3'-UTR of glycine N-methyltransferaseto and impacts the proliferation and invasion of HCC, and exosomal miR-224 may be used as a potential diagnostic and prognostic factor for patients with HCC.

Research perspectives

Our study provides novel insight into the mechanism of exosomal miR-224 in the development and invasion of HCC and may provide a potential biomarker for the diagnosis and prognosis of HCC.