title: PAX3 is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells.
abstract: Paired box 3 (PAX3) is overexpressed in glioma tissues compared to normal brain tissues, however, the pathogenic role of PAX3 in human glioma cells remains to be elucidated. In this study, we selected the human glioma cell lines U251, U87, SHG-44, and the normal human astrocytes, 1800, which have differential PAX3 expression depending upon the person. SiRNA targeting PAX3 and PAX3 overexpression vectors were transfected into U87 and SHG-44 glioma cell lines, and cell proliferation, invasion, apoptosis, and differentiation were examined by CCK-8 assays, transwell chamber assays, tunnel staining, Annexin V/PI analysis, and Western blotting, respectively. In addition, we used subcutaneous tumor models to study the effect of PAX3 on the growth of glioma cells in vivo. We found that PAX3 was upregulated in the three glioma cell lines. PAX3 knockdown inhibited cell proliferation and invasion, and induced apoptosis in the U87MG glioblastoma cell line, whereas PAX3 upregulation promoted proliferation, inhibited apoptosis, and increased invasion in the SHG-44 glioma cell line. Moreover, we found that targeting PAX3 expression in glioma cell lines together with chemotherapeutic treatment could increase glioma cell susceptibility to the drug. In subcutaneous tumor models in nude mice using glioma cell lines U-87MG and SHG-44, inhibition of PAX3 expression in glioblastoma U-87MG cells suppressed tumorigenicity, and upregulation of PAX3 expression in glioma SHG-44 cells promoted tumor formation in vivo. These results indicate that PAX3 in glioma is essential for gliomagenesis; thus, targeting PAX3 or its downstream targets may lead to novel therapies for this disease.
authors.affiliation: Department of Neurosurgery, Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xia
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Huang
authors.forename: Dekang
authors.initials: D
authors.lastname: Nie
authors.forename: Jinlong
authors.initials: J
authors.lastname: Shi
authors.forename: Mingjie
authors.initials: M
authors.lastname: Gong
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.forename: Peipei
authors.initials: P
authors.lastname: Gong
authors.forename: Longxiang
authors.initials: L
authors.lastname: Zhao
authors.forename: Hao
authors.initials: H
authors.lastname: Zuo
authors.forename: Shaoqin
authors.initials: S
authors.lastname: Ju
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005260:Female; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000096:biosynthesis*; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D034741:RNA, Small Interfering