PAX3Is Overexpressed In Human Glioblastomas And Critically Regulates The Tumorigenicity Of Glioma Cells

Part one:The Expression and Clinical Significance of Pax3in Human GliomasObjective Transcription factors initiate a program of gene expression and are catalysts in downstream molecular cascades that modulate a variety of cellular processes. PAX3is a transcription factor which plays key roles in several human malignancies. In this study, we investigated the expressions of PAX3in human gliomas and its relationship with malignant degree.Methods Fifty seven cases of gliomas and ten cases of normal brain tissues were collected and were divided into several groups by pathological grade. The expressions of PAX3were measured by PCR in mRNA level and by western blot and immunohistochemisty in protein level. PAX3levels between normal brain tissues and glioma tissues were analyzed by statistics.Results PCR, the expression level of PAX3mRNA in glioma was higher than that in nomal brain tissues (P<0.05). As the same, in western blotting and immunohistochemistry, the expression level of PAX3in glioma is higher than that in nomal brain tissues (P<0.05). The expression of PAX3was correlated with the pathological grade of gliomas.Conclusions PAX3might play a key role in the onset and process of glioma.It could be used as an assistant diagnostic index for glioma. Part two:PAX3Overexpression Is Oncogenic In GliomaBackground Paired box3(PAX3) is overexpressed in glioma tissues compared to normal brain tissues. However, the pathogenic role of PAX3in human glioma cells remains to be elucidated.Methods We selected the human glioma cell lines U251, U87, SHG-44, and the normal human astrocytes,1800, which have differential PAX3expression depending upon the person. SiRNA targeting PAX3and PAX3overexpression vectors were transfected into U87and SHG-44glioma cell lines, and cell proliferation, invasion, apoptosis, and differentiation were examined by CCK-8assays, transwell chamber assays, and Western blotting, respectively. In addition, we used subcutaneous tumor models to study the effect of PAX3on the growth of glioma cells in vivo.Results We found that PAX3was upregulated in the three glioma cell lines. PAX3knockdown inhibited cell proliferation and invasion, and induced apoptosis in the U87MG glioblastoma cell line, whereas PAX3upregulation promoted proliferation, inhibited apoptosis, and increased invasion in the SHG-44glioma cell line. Moreover, in subcutaneous tumor models in nude mice using glioma cell lines U-87MG and SHG-44, inhibition of PAX3expression in glioblastoma U-87MG cells suppressed turnorigenicity, and upregulation of PAX3expression in glioma SHG-44cells promoted tumor formation in vivo.Conclusions These results indicate that PAX3in glioma is essential for gliomagenesis; thus, targeting PAX3or its downstream targets may lead to novel therapies for this disease.