MEG3/miR‑21 axis affects cell mobility by suppressing epithelial‑mesenchymal transition in gastric cancer
Authors: Kun Zhu
Dawei Yuan
Lei Meng
Yong Zhang
Gang Xu
Kang Li
Chengxue Dang
Journal: Oncology Reports (2018)
Discipline: CLINICAL MEDICINE
Keywords: Gastric cancer; MEG3; miR-21; cell mobility; tumor progression
Affiliations: Department of Surgical Oncology, First Afﬁliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

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. 

Retracted: No

PubPeer comments:
 Fig 2B.  MEG3 inhibits the invasion and migration of gastric cancer cells by suppressing EMT. AGS cells were transfected with MEG3 scramble or lncRNA-MEG3, respectively, with non-transfected AGS cells as the control group.... (B and C) Invasion ability of the cells was assayed by Transwell model . Control and MEG3-scramble panels overlap after a 180-deg flip. ![file] Also overlaps with Fig 1D of [Tian et al (2018)] ... ![] ...and Fig 2E from [Jiang et al (2018)] . ![] Meanwhile, lncRNA-MEG panel overlaps with the righthand panel of 1C of Tian et al (2018). ![file] , 
 Figs 2D, 3E. Duplicated panels marked. ![file] , 
 The Control and lncRNA-MEG3 panels of Fig 2B also overlap with corresponding panels in *[below]* 3G, which is perhaps legitimate. ![] But the miR-21-mimic panel of 3G *[red rectangle]* is the same as Fig 3B from [Li et al (2018)] ,  LNCap and PC-3 cells were transfected with SChLAP1- siRNA or scramble ... ![] ...and the miR-184 mimic panel from Fig 4A of [Li et al (2018b)] . ![] Perhaps not so legitimate. ,