Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 21, 2021; 27(3): 240-254
Published online Jan 21, 2021. doi: 10.3748/wjg.v27.i3.240
Circular RNA AKT3 governs malignant behaviors of esophageal cancer cells by sponging miR-17-5p
Hong-Liang Zang, Fu-Jian Ji, Hai-Ying Ju, Xiao-Feng Tian
Hong-Liang Zang, Xiao-Feng Tian, Department of Hepatobiliary and Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
Fu-Jian Ji, Department of Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
Hai-Ying Ju, Department of Hematology, Jilin Province Blood Center, Changchun 130000, Jilin Province, China
Author contributions: Zang HL contributed to the study design and reviewed the manuscript; Ji FJ and Tian XF analyzed the data and wrote the manuscript; Ju HY and Zang HL contributed to the data collection, data interpretation, and manuscript writing; all authors read and approved the final manuscript.
Institutional review board statement: This research was reviewed and approved by the Ethics Committee of China-Japan Union Hospital of Jilin University and complied with the guidelines of Declaration of Helsinki.
Institutional animal care and use committee statement: The procedures were in accordance with guidelines of Animal Use and Care Committee of China-Japan Union Hospital of Jilin University.
Conflict-of-interest statement: All the authors have no conflict of interest related to the manuscript.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: Xiao-Feng Tian, MD, Chief Doctor, Department of Hepatobiliary and Pancreatic Surgery, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Erdao District, Changchun 130033, Jilin Province, China. fengwykctut4210@163.com
Received: October 30, 2020
Peer-review started: October 30, 2020
First decision: November 30, 2020
Revised: December 4, 2020
Accepted: December 16, 2020
Article in press: December 16, 2020
Published online: January 21, 2021
Abstract
BACKGROUND

Recent studies have demonstrated that circular RNA AKT3 (circAKT3) plays a crucial role in regulating the malignant phenotypes of tumor cells. However, the potential effects of circAKT3 on esophageal cancer have not been investigated.

AIM

To illuminate the role of circAKT3 in malignant behaviors of esophageal cancer cells and its underlying mechanism.

METHODS

Clinical samples were collected to detect the expression of circAKT3. The role of circAKT3 in proliferation, migration, invasion, and apoptosis of esophageal cancer cells was evaluated using Cell Counting Kit-8, wound healing assays, Transwell assays, and fluorescence analysis, respectively. The target of circAKT3 was screened and identified using an online database and luciferase reporter assay. A xenograft nude mouse model was established to investigate the role of circAKT3 in vivo.

RESULTS

In vitro assays showed that proliferative, migratory, and invasive capacities of esophageal cancer cells were significantly enhanced by circAKT3 overexpression. Furthermore, miR-17-5p was screened as the target of circAKT3, and miR-17-5p antagonized the effects of circAKT3 on esophageal cancer cells. Moreover, we identified RHOC and STAT3 as the direct target molecules of miR-17-5p, and circAKT3 facilitated expression of RHOC and STAT3 by inhibiting miR-17-5p. In vivo assays showed circAKT3 knockdown inhibited growth of esophageal cancer.

CONCLUSION

CircAKT3 contributed to the malignant behaviors of esophageal cancer in vitro and in vivo by sponging miR-17-5p thus providing a potential target for treatment of esophageal cancer.

Keywords: Esophageal cancer, Circular RNA AKT3, miR-17-5p, Proliferation, Migration, Invasion

Core Tip: Circular RNA AKT3 was overexpressed in esophageal cancer and enhanced proliferative, migratory, and invasive capacities of esophageal cancer cells by sponging miR-17-5p to exert protumor effects. Downregulation of circular RNA AKT3 inhibited xenograft tumor growth of esophageal cancer in vivo. This research provided a potential target for better understanding the underlying mechanism of esophageal cancer.