LncRNA MEG3 inhibits the progression of prostate cancer by facilitating H3K27 trimethylation of EN2 through binding to EZH2.

This study aims to study the effects of intra-nuclear lncRNA MEG3 on the progression of prostate cancer and the underlying mechanisms. Expressions of relative molecules were detected by Quantitative real time PCR (qRT-PCR) and western blot. Chromatin immunoprecipitation and RNA immunoprecipitation (RIP) assays were used to evaluate the interaction between intra-nuclear MEG3, histone methyltransferase EZH2 and Engrailed-2 (EN2). The impacts of MEG3 on the viability, proliferation and invasion of prostate cancer cells (PC3) were evaluated by methyl thiazolyl tetrazolium, colony formation and transwell assays, respectively. PC3 cells were transfected with MEG3 and transplanted into nude mice to analyse the effect of MEG3 on tumourigenesis of PC3 cells in vivo. EN2 expression was inversely proportional to MEG3 in the prostate cancer tissues and PC3 cells. RIP results showed that intra-nuclear MEG3 could bind to EZH2. Knockdown of MEG3 and/or EZH2 up-regulated EN2 expression and reduced the recruitment of EZH2 and H3K27me3 to EN2, while over-expressed MEG3 caused opposite effects. MEG3 over-expression suppressed cell viability, colony formation, cell invasion and migration of PC3 cells in vitro and inhibited tumourigenesis of PC3 cells in vivo, while EN2 over-expression diminished the effects. These findings indicated that MEG3 facilitated H3K27 trimethylation of EN2 via binding to EZH2, thus suppressed the development of prostate cancer.

Zhou Y ，Yang H ，Xia W ，Cui L ，Xu R ，Lu H ，Xue D ，Tian Z ，Ding T ，Cao Y ，Shi Q ，He X ... -  《-》

Long Noncoding RNA Meg3 Regulates Mafa Expression in Mouse Beta Cells by Inactivating Rad21, Smc3 or Sin3α.

The main pathogenic mechanism of diabetes is a decrease in the number of islet beta cells or a decline in their function. Recent studies have shown that pancreatic long noncoding RNAs (lncRNAs) have a high degree of tissue specificity and may be involved in the maintenance of islet cells function and the development of diabetes. The aim of this study was to investigate the molecular regulatory mechanism of mouse maternal expressed gene 3 (Meg3) in insulin biosynthesis in pancreatic islets. Chromatin immunoprecipitation-quantitative polymerase chain reaction (qPCR) and RNA immunoprecipitation-qPCR were used to investigate the molecular mechanism of lncRNA Meg3 in insulin biosynthesis by regulating v-Maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MafA), a mature beta cell marker in the MIN6 beta cell line. Further, the expression levels of Meg3, Ezh2, MafA, Rad21, Smc3, and Sin3α were analyzed in vivo and in vitro by RT-PCR and western blotting. Intranuclear lncRNA Meg3 can bind EZH2, a methyltransferase belonging to the Polycomb repressive complex-2, in pancreatic islet cells. In addition, knockdown of Ezh2 can also inhibit the expression of MafA and Ins2, while expression levels of Rad21, Smc3, and Sin3α are upregulated, by interfering with Ezh2 or Meg3 in pancreatic beta cells. Knockdown of Meg3 resulted in the loss of EZH2 binding and H3K27 trimethylation occupancy of Rad21, Smc3, and Sin3α promoter regions. The inhibition of Rad21, Smc3, or Sin3α, which directly act on the MafA promoter, leads to upregulated expression of MafA in both MIN6 cells and mouse islets. Moreover, the synthesis and secretion of insulin were increased by inhibition of these transcription factors. Pancreatic lncRNA Meg3 can epigenetically regulate the expression of Rad21, Smc3, and Sin3α via EZH2-driven H3K27 methylation. By inhibiting the expression of Rad21, Smc3, or Sin3α, Meg3 promotes the expression of MafA and affects the production of insulin.

Wang N ，Zhu Y ，Xie M ，Wang L ，Jin F ，Li Y ，Yuan Q ，De W ... -  《-》

Involvement of aberrantly activated HOTAIR/EZH2/miR-193a feedback loop in progression of prostate cancer.

Ling Z ，Wang X ，Tao T ，Zhang L ，Guan H ，You Z ，Lu K ，Zhang G ，Chen S ，Wu J ，Qian J ，Liu H ，Xu B ，Chen M ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

LncRNA XIST facilitates cell growth, migration and invasion via modulating H3 histone methylation of DKK1 in neuroblastoma.

Zhang J ，Li WY ，Yang Y ，Yan LZ ，Zhang SY ，He J ，Wang JX ... -  《-》

Tumor suppressive lncRNA MEG3 binds to EZH2 and enhances CXCL3 methylation in gallbladder cancer.

Li DQ ，Ding YR ，Che JH ，Su Z ，Yang WZ ，Xu L ，Li YJ ，Wang HH ，Zhou WY ... -  《-》