55384

MEG3

Histone methylation is implicated in a number of biological and pathological processes, including cancer development. In this study, we investigated the molecular mechanism for the recruitment of Polycomb repressive complex-2 (PRC2) and its accessory component, JARID2, to chromatin, which regulates methylation of lysine 27 of histone H3 (H3K27), during epithelial-mesenchymal transition (EMT) of cancer cells. The expression of MEG3 long noncoding RNA (lncRNA), which could interact with JARID2, was clearly increased during transforming growth factor-beta (TGF-beta)-induced EMT of human lung cancer cell lines. Knockdown of MEG3 inhibited TGF-beta-mediated changes in cell morphology and cell motility characteristic of EMT and counteracted TGF-beta-dependent changes in the expression of EMT-related genes such as CDH1, ZEB family, and the microRNA-200 family. Overexpression of MEG3 influenced the expression of these genes and enhanced the effects of TGF-beta in their expressions. Chromatin immunoprecipitation (ChIP) revealed that MEG3 regulated the recruitment of JARID2 and EZH2 and histone H3 methylation on the regulatory regions of CDH1 and microRNA-200 family genes for transcriptional repression. RNA immunoprecipitation and chromatin isolation by RNA purification assays indicated that MEG3 could associate with JARID2 and the regulatory regions of target genes to recruit the complex. This study demonstrated a crucial role of MEG3 lncRNA in the epigenetic regulation of the EMT process in lung cancer cells.CI - (c) 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

A growing body of evidence suggests that the dysregulation of long noncoding RNA is increasingly linked to many human diseases. Maternally expressed gene 3 ( MEG3) is one such gene thought to be affected. In the placenta of patients with preeclampsia, there is reduced expression of MEG3; however, its role and the mechanism involved are not clear. Therefore, we examined the expression of MEG3, epithelial-mesenchymal transition (EMT) markers (E-cadherin and N-cadherin), and TGF-beta/smad signaling pathway genes ( TGF-beta1, smad3, and smad7) in the placental tissues of 20 patients with preeclampsia and 20 healthy patients. We further observed the impact of MEG3 on the invasion and migration functions of human trophoblast cells and the effects on EMT and TGF-beta/smad signaling pathways in an Human trophoblast cell-8 (HTR-8)Vneo cell line. The expression of MEG3 was lower in tissues from patients with preeclampsia having an EMT decline, as well as a messenger RNA expression of smad7. The expression of TGF-beta1 and smad3 were higher in patients with preeclampsia. In HTR-8/SVneo cells with overexpressed MEG3, the invasion and migration functions were enhanced and accompanied by higher EMT and a significantly increased expression of smad7. Our data indicate that MEG3 is closely associated with the pathogenesis of preeclampsia and thus associated with changes in the EMT of placental trophoblast cells. These results indicate that MEG3 regulation of trophoblast cell EMT via the TGF-beta pathway inhibitor smad7 may be the molecular mechanism involved in the pathogenesis of preeclampsia.

The prognosis of patients with gastric cancer remains poor mainly due to distant metastasis. Maternally expressed gene 3 (MEG3), a long noncoding RNA (lncRNA), is downregulated in various tumor tissues and suppresses tumor progression. miR21 is a microRNA which is expressed highly in tumor tissues. In the present study, we investigated the relationship between MEG3 and miR21 in regards to the cell mobility of gastric cancer. Our data demonstrated that MEG3 was downregulated while miR21 was upregulated in gastric cancer tissues and cell lines by qRTPCR. Overexpression of MEG3 suppressed cell mobility of gastric cancer cells (AGS) by downregulating the expression of MMP3, MMP9 and VEGF. As shown by western blot analysis, overexpression of MEG3 also suppressed epithelialmesenchymal transition (EMT) by increasing the expression of an epithelial marker (Ecadherin) and downregulating the expression of mesenchymal markers (Ncadherin, Snail and betacatenin), indicating that MEG3 suppressed cell mobility through the inhibition of EMT in gastric cancer. The expression of miR21 was negatively regulated by MEG3 and overexpression of miR21 promoted cell mobility of AGS through activation of EMT. Cotransfection of lncRNAMEG3 and miR21 mimic counteracted the inhibitory effect on the cell mobility attributed to MEG3, suggesting that the MEG3/miR21 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 miR21 had the opposite effects. The MEG3/miR21 axis affected gastric cancer growth and metastasis through inhibition of EMT in vivo. In conclusion, we demonstrated that the MEG3/miR21 axis participates in the tumor progression and metastasis of gastric cancer through the regulation of EMT.