MEG3/miR‑21 axis affects cell mobility by suppressing epithelial‑mesenchymal transition in gastric cancer

Xu,Gang; Meng,Lei; Yuan,Dawei; Li,Kang; Zhang,Yong; Dang,Chengxue; Zhu,Kun

doi:10.3892/or.2018.6424

MEG3/miR‑21 axis affects cell mobility by suppressing epithelial‑mesenchymal transition in gastric cancer

Authors:
- Gang Xu
- Lei Meng
- Dawei Yuan
- Kang Li
- Yong Zhang
- Chengxue Dang
- Kun Zhu
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Affiliations: Department of Surgical Oncology, First Afﬁliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: May 8, 2018 https://doi.org/10.3892/or.2018.6424
Pages: 39-48
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The prognosis of patients with gastric cancer remains poor mainly due to distant metastasis. Maternally expressed gene 3 (MEG3), a long non‑coding RNA (lncRNA), is downregulated in various tumor tissues and suppresses tumor progression. miR‑21 is a microRNA which is expressed highly in tumor tissues. In the present study, we investigated the relationship between MEG3 and miR‑21 in regards to the cell mobility of gastric cancer. Our data demonstrated that MEG3 was downregulated while miR‑21 was upregulated in gastric cancer tissues and cell lines by qRT‑PCR. Overexpression of MEG3 suppressed cell mobility of gastric cancer cells (AGS) by downregulating the expression of MMP‑3, MMP‑9 and VEGF. As shown by western blot analysis, overexpression of MEG3 also suppressed epithelial‑mesenchymal transition (EMT) by increasing the expression of an epithelial marker (E‑cadherin) and downregulating the expression of mesenchymal markers (N‑cadherin, Snail and β‑catenin), indicating that MEG3 suppressed cell mobility through the inhibition of EMT in gastric cancer. The expression of miR‑21 was negatively regulated by MEG3 and overexpression of miR‑21 promoted cell mobility of AGS through activation of EMT. Co‑transfection of lncRNA‑MEG3 and miR‑21 mimic counteracted the inhibitory effect on the cell mobility attributed to MEG3, suggesting that the MEG3/miR‑21 axis affects cell mobility by suppressing EMT in gastric cancer. Using a mouse xenograft tumor model, we found that the overexpression of MEG3 suppressed tumor growth and metastasis while overexpression of miR‑21 had the opposite effects. The MEG3/miR‑21 axis affected gastric cancer growth and metastasis through inhibition of EMT in vivo. In conclusion, we demonstrated that the MEG3/miR‑21 axis participates in the tumor progression and metastasis of gastric cancer through the regulation of EMT.

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