Expression Of MEF2D In Human Glioma And Its Effects On The Proliferation And Migration Of Glioma Cells

Objective:Glioma is the most common primary brain tumors, which formed a certain relationship with environment factors and genetic mutants; the latter includes the collaborative effects of a variety of oncogenes or tumor suppressor genes. Myocyte enhancer factor 2(MEF2) families, as transcription factors, play important roles in the survival of different types of cells through regulation of survival/death related genes. Furthermore, MEF2 D is proved to play a role in the regulation of cell proliferation, migration and invasion. Researches in the central nervous system(CNS) show that, MEF2 D has an important regulatory role in neuronal survival, underlying the pathogenesis of Parkinson’s disease. In nasopharyngeal carcinoma and hepatocellular carcinoma, MEF2 D acts as an oncogene participating in development of tumor, but in rhabdomyosarcoma, almost no expression or low expression of MEF2 D is detected, while up-regulation of MEF2 D significantly inhibits tumor proliferation and growth, hinting that MEF2 D is a tumor suppressive gene. Although previous studies about MEF2 D have been involved in tumors and CNS, the role of MEF2 D in human glioma is still unclear. Therefore, this experiment was designed to investigate the expression of MEF2 D in clinical human glioma specimens using immunohistochemistry and Western blot analysis. Furthermore, with down-regulation of MEF2 D level in human malignant glioblastoma(U87MG) cells, the impact of MEF2 D on the proliferation and migration of U87 MG cells have been investigated.Method:(1)To collect glioma specimens and investigate the expression of MEF2 D in clinical human glioma specimens with immunohistochemistry and Western blot analysis.(2)The expression level of MEF2 D in U87 MG cell lines was observed with immunofluorescence analysis while the U87 MG cells were infected with MEF2D-sh RNA lentivirus viron and endogenous expression level of MEF2 D in U87 MG cells were suppressed;(3)The effects of MEF2 D on the proliferation and migration in U87 MG cell were evaluated by proliferation and scratch assay in U87 MG cell lines.Results:(1)Immunohistochemical and Western blot results indicate that MEF2 D level in high-grade gliomas was significantly higher than that in low-grade gliomas and control brain tissue, there is a statistically significant difference.(2)Immunofluorescence staining showed that U87 MG cells have a constitutive gene expression of MEF2 D, but this expression can be successfully inhibited by MEF2D-sh RNA lentivirus infection in U87 MG cells.(3)Compared with control group(U87) and negative control group(NC), proliferation and migration ability in MEF2D-sh RNA group significantly decreased, the difference is statistically significant.Conclusion :(1)Myocyte enhancer factor transcriptional 2D(MEF2D) exists in malignant glioma and increasing of MEF2 D expression levels in human glioma tissues were positively correlated with pathological grade of glioma, hinting that MEF2 D may be involved in the occurrence and development of glioma cancer genes.(2)Down-regulation of MEF2 D can effectively inhibit the proliferation activity and migration of U87 MG cells, suggesting MEF2 D may be a potential target for gene therapy of gliomas.