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microRNA-582 Potentiates Liver and Lung Metastasis of Gastric Carcinoma Cells Through the FOXO3-Mediated PI3K/Akt/Snail Pathway

Authors Xie T, Wu D, Li S, Li X, Wang L, Lu Y, Song Q, Sun X, Wang X

Received 11 January 2020

Accepted for publication 30 May 2020

Published 30 June 2020 Volume 2020:12 Pages 5201—5212

DOI https://doi.org/10.2147/CMAR.S245674

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Eileen O'Reilly


Tianyu Xie,1,2 Di Wu,2 Shuo Li,1,2 Xiongguang Li,1,2 Lipeng Wang,2 Yixun Lu,2 Qiying Song,2 Xuehong Sun,2 Xinxin Wang1,2

1School of Medicine, Nankai University, Tianjin 300071, People’s Republic of China; 2Department of General Surgery, Chinese PLA General Hospital, Beijing 100853, People’s Republic of China

Correspondence: Xinxin Wang Tel/ Fax +86-10-66938328
Email xinxinwang1111@163.com

Background: The dysregulation of microRNA (miRNAs) is broadly participated in cancer progression, resulting in sustained cell proliferation by directly targeting various targets. This study investigated the expression of miR-582 in GC and its association with liver metastasis.
Methods: Firstly, differentially expressed miRNAs in gastric cancer (GC) tissues were predicted by microarray. Then, the relationship between miR-582 and clinical characteristics of GC patients was analyzed. By silencing of miR-582 in GC cells, the change in malignant biological behaviors of GC cells was detected. The upstream lncRNA, downstream targeting genes of miR-582 and the corresponding signaling pathway were predicted by online databases and verified by luciferase reporter assays, RT-qPCR and Western blot analysis. Finally, the effects of miR-582 on the growth and metastasis of GC cells were detected by in vivo tumorigenesis and metastasis tests.
Results: MiR-582 was highly expressed in GC tissues and related to the metastasis of patients with GC. Silencing of miR-582 expression blocked malignant biological behaviors of GC cells in vitro and in vivo. MiR-582 inhibited forkhead box protein O3 (FOXO3) to upregulate the PI3K/AKT/Snail signaling pathway in GC cells. Besides, GATA6-AS1 was found as an upstream lncRNA to modulate the expression of miR-582.
Conclusion: MiR-582 induced by GATA6-AS1 silencing promotes the growth and metastasis of GC cells by targeting FOXO3 to induce the activation of the PI3K/AKT/Snail signaling pathway. MiR-582 could be a potential molecular therapy target for patients with GC.

Keywords: gastric cancer, miR-582, PI3K/AKT/Snail signaling pathway, proliferation, metastasis, tumorigenesis

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