ISSN |
1948-0210 (online) |
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/ |
Copyright |
© The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved. |
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Publisher |
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA |
Website |
http://www.wjgnet.com |
Category |
Oncology |
Manuscript Type |
Basic Study |
Article Title |
miR-3682-3p directly targets FOXO3 and stimulates tumor stemness in hepatocellular carcinoma via a positive feedback loop involving FOXO3/PI3K/AKT/c-Myc
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Manuscript Source |
Unsolicited Manuscript |
All Author List |
Qian Chen, Si-Bo Yang, Ye-Wei Zhang, Si-Yuan Han, Lei Jia, Bo Li, Yi Zhang and Shi Zuo |
ORCID |
|
Funding Agency and Grant Number |
Funding Agency |
Grant Number |
the 12th Special Fund for Young Scientists and Technicians in Guizhou Province |
(2019) 5647 |
the Science and Technology Fund of Guizhou Provincial Health and Health Commission |
gzwjkj2020-1-101 |
the National Natural Science Foundation Training Program of Guizhou Medical University |
19NSP055 |
Dongguan Science and Technology of Social Development Program |
201950715024201 |
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Corresponding Author |
Shi Zuo, PhD, Chief Doctor, Department of Hepatobiliary Surgery, Affiliated Hospital of Guizhou Medical University, No. 28 Gui Medical Street, Beijing Road, Yunyan District, Guiyang 550000, Guizhou Province, China. 1056659393@qq.com |
Key Words |
miR-3682-3p; FOXO3; Cancer stem cells; Hepatocellular carcinoma |
Core Tip |
In this work, we identified miR-3682-3p as a key inducer of cancer stem cell properties, thereby promoting the pathogenesis of hepatocellular carcinoma (HCC). In brief, we found that the upregulation of miR-3682-3p enhanced the spheroid forming ability, the fraction of side population cells, and the expression of cancer stem cell factors in HCC cells in vitro as well as the tumorigenicity of transplanted HCC cells in vivo; furthermore, silencing miR-3682-3p significantly prolonged the survival time of HCC-bearing mice. Mechanistically, we found that miR-3682-3p targets FOXO3 and enables FOXO3/β-catenin interaction, which promotes c-Myc expression through PI3K/AKT; c-Myc, in turn, activates miR-3682-3p, resulting in the formation of a positive feedback loop. Taken together, we identified a novel positive feedback regulatory loop involving HBx, miR-3682-3p, FOXO3, β-catenin, and c-Myc that plays a pivotal role in the stemness of HCC. Our findings revealed a novel mechanism by which miR-3682-3p promotes stem cell maintenance in HCC, and silencing miR-3682-3p may represent a novel therapeutic strategy for the treatment of this cancer. |
Publish Date |
2022-07-26 11:15 |
Citation |
Chen Q, Yang SB, Zhang YW, Jia L, Li B, Zhang Y, Zuo S. miR-3682-3p directly targets FOXO3 and stimulates tumor stemness in hepatocellular carcinoma via a positive feedback loop involving FOXO3/PI3K/AKT/c-Myc. World J Stem Cells 2022; 14(7): 539-555 |
URL |
https://www.wjgnet.com/1948-0210/full/v14/i7/539.htm |
DOI |
https://dx.doi.org/10.4252/wjsc.v14.i7.539 |