Cancer Management and Research (Jun 2020)

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

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

Journal volume & issue
Vol. Volume 12
pp. 5201 – 5212

Abstract

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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 ChinaCorrespondence: Xinxin Wang Tel/ Fax +86-10-66938328Email [email protected]: 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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