Publication Name	World Journal of Stem Cells
Manuscript ID	76194
Country	China

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
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
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
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.
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

Received	2022-03-06 14:34
Peer-Review Started	2022-03-06 14:36
To Make the First Decision
Return for Revision	2022-04-19 02:09
Revised	2022-04-24 14:14
Second Decision	2022-06-20 03:01
Accepted by Journal Editor-in-Chief
Accepted by Company Editor-in-Chief	2022-06-26 23:44
Articles in Press	2022-06-26 23:44
Publication Fee Transferred
Edit the Manuscript by Language Editor
Typeset the Manuscript	2022-07-22 07:50

ISSN	1948-0210 (online)
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