Maternally expressed gene 3 regulates retinal neovascularization in retinopathy of prematurity

The mouse model of oxygen induced retinopathy is suitable for the study of various retinal neovascularization diseases,including retinopathy of prematurity.The maternally expressed gene 3(MEG3)has been demonstrated to have an inhibitory effect on diabetic retinopathy.In this study,we investigated the role of MEG3 overexpression in oxygen-induced retinopathy in mice.The results showed that MEG3 overexpression effectively inhibited the production of retinal neovascularization in oxygen-induced retinopathy mice.It acts by down-regulating the expression of phosphoinositide 3-kinase,serine/threonine kinase,and vascular endothelial growth factor and pro-inflammatory factors.MEG3 overexpression lentivirus has a future as a new method for the clinical treatment of retinopathy of prematurity.The animal experiments were approved by the Animal Ethics Committee of Shengjing Hospital of China Medical University,China(approval No.2016PS074K)on February 25,2016.

LncRNA MEG3 Inhibits the Epithelial-mesenchymal Transition of Bladder Cancer Cells through the Snail/E-cadherin Axis

Objective This study aimed to investigate the role of the long noncoding RNA(lncRNA)maternally expressed gene 3(MEG3)in the epithelial-mesenchymal transition(EMT)of bladder cancer cells and the potential mechanisms.Methods Cell invasion,migration,and wound healing assays were conducted to assess the effects of MEG3 on the invasive and migratory capabilities of bladder cancer cells.The expression levels of E-cadherin were measured using Western blotting,RT-qPCR,and dual luciferase reporter assays.RNA immunoprecipitation and pull-down assays were performed to investigate the interactions between MEG3 and its downstream targets.Results MEG3 suppressed the invasion and migration of bladder cancer cells and modulated the transcription of E-cadherin.The binding of MEG3 to the zinc finger region of the transcription factor Snail prevented its ability to transcriptionally repress E-cadherin.Additionally,MEG3 suppressed the phosphorylation of extracellular regulated protein kinase(ERK),c-Jun N-terminal kinase(JNK),and P38,thereby decreasing the expression of Snail and stimulating the expression of E-cadherin.Conclusion MEG3 plays a vital role in suppressing the EMT in bladder cancer cells,indicating its potential as a promising therapeutic target for the treatment of bladder cancer.

Zbed3 participates in the subcortical maternal complex and regulates the distribution of organelles

We previously identified a subcortical maternal complex （SCMC） that is essential for early embryogenesis and female fertility in mice. However, the molecular mechanism by which the SCMC affects female fertility remains largely uncharacterized. Here, we report that a novel maternal protein, zinc finger BED-type containing 3 （Zbed3）, participates in the SCMC. Depletion of maternal Zbed3 results in reduced fecundity of females, because of the impaired and delayed development in a proportion of mutant embryos. The loss of maternal Zbed3 results in asymmetric zygotic division and abnormal distributions of organeUes in the affected oocytes and zygotes, similar to the phenotypes observed in females with disrupted core SCMC genes. Further investiga- tion revealed that these phenotypes are associated with disrupted dynamics of microtubules and/or formation of cytoplasmic lat- tices （CPLs）. The stability and localization of Zbed3 depend on, but are not required for, the formation of the SCMC. Thus, our data suggest Zbed3 as one of downstream proteins mediating SCMC functions and provide further insights into the roles of the SCMC and CPLs in female fertility.

Macrophage migration inhibitory factor protects bone marrow mesenchymal stem cells from hypoxia/ischemia-induced apoptosis by regulating lncRNA

Objective:This research was performed to explore the effect of macrophage migration inhibitory factor(MIF)on the apoptosis of bone marrow mesenchymal stem cells(BMSCs)in ischemia and hypoxia environments.Methods:The cell viability of BMSCs incubated under hypoxia/ischemia(H/I)conditions with or without pretreatment with MIF or triglycidyl isocyanurate(TGIC)was detected using cell counting kit-8(CCK-8)analysis.Plasmids containing long noncoding RNA(lncRNA)maternally expressed gene 3(MEG3)orβ-catenin small interfering RNA(siRNA)were used to overexpress or downregulate the corresponding gene,and the p53 signaling pathway was activated by pretreatment with TGIC.The influences of MIF,overexpression of lncRNA MEG3,activation of the p53 signaling pathway,and silencing ofβ-catenin on H/I-induced apoptosis of BMSCs were revealed by western blotting,flow cytometry,and terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labeling(TUNEL)staining.Results:From the results of CCK-8 assay,western blotting,and flow cytometry,pretreatment with MIF significantly decreased the H/I-induced apoptosis of BMSCs.This effect was inhibited when lncRNA MEG3 was overexpressed by plasmids containing MEG3.The p53 signaling pathway was activated by TGIC,andβ-catenin was silenced by siRNA.From western blot results,the expression levels ofβ-catenin in the nucleus and phosphorylated p53(p-p53)were downregulated and upregulated,respectively,when the lncRNA MEG3 was overexpressed.Through flow cytometry,MIF was also shown to significantly alleviate the increased reactive oxygen species(ROS)level of BMSCs caused by H/I.Conclusions:In summary,we conclude that MIF protected BMSCs from H/I-induced apoptosis by downregulating the lncRNA MEG3/p53 signaling pathway,activating the Wnt/β-catenin signaling pathway,and decreasing ROS levels.