title: GFAP expression is regulated by Pax3 in brain glioma stem cells.
abstract: Glioblastomas are understood to evolve from brain glioma stem cells (BGSCs), and yet the biology underlying this model of tumorigenesis is largely unknown. Paired box 3 protein (Pax3) is a member of the paired box (Pax) family of transcription factors that is normally expressed during embryonic development, but has recently been implicated in tumorigenesis. The present study demonstrated that Pax3 is differentially expressed in U87MG human glioma cell, BGSC and normal 1800 human astrocyte lines. Herein, we identified that the glial fibrillary acidic protein (GFAP), a major intermediate filament protein of mature astrocytes, is directly downregulated during the differentiation of BGSCs via the binding of Pax3 to the promoter region of GFAP. Moreover, siRNA silencing of Pax3 arrested BGSC differentiation, while overexpression of Pax3 promoted the differentiation in BGSCs. Furthermore, we studied the cell proliferation, invasion, apoptosis, differentiation and expression of Pax3 and GFAP in Pax3 siRNA-knockdown and Pax3-overexpressing BGSC models by CCK-8, Transwell migration, flow cytometry and western blot assays. The results indicate that Pax3 regulates GFAP expression, and that Pax3 may contribute to the evolution of BGSCs towards malignancy.
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Xing
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Lanchun
authors.initials: L
authors.lastname: Ni
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Zhikai
authors.initials: Z
authors.lastname: Gu
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Yilu
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Huang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics*; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D000072041:PAX3 Transcription Factor / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D005904:Glial Fibrillary Acidic Protein; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D034741:RNA, Small Interfering