title: Knockdown of nuclear factor erythroid 2-related factor 2 by lentivirus induces differentiation of glioma stem-like cells.
abstract: Glioma stem cells (GSCs) are key in the progression and recurrence of glioblastoma. Inducing the differentiation of GSCs is an important therapeutic target for glioblastoma. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been reported to be important in maintaining the stem cell status of GSCs; however, its association with differentiation has not been studied. Herein, we knocked down Nrf2 from GSCs to investigate the role of Nrf2 in the differentiation of GSCs. First, Nrf2 expression was observed at different stages of differentiation; then, Nrf2 was knocked down and the association of Nrf2 with differentiation degree was observed in vitro. Finally, GSCs were planted in nude mice to study the association of Nrf2 with differentiation in vivo. The expression of Nrf2 decreased with the differentiation process. Following Nrf2 knockdown, the proportion of sphere-like colonies decreased and the dendritic cells in spheres increased; the expression of Nrf2 significantly decreased while the expression of differentiation marker glial fibrillary acidic protein (GFAP) and βIII-tubulin increased both at the protein and the gene level. In the xenografts of nude mice, the differentiation of tumor cells was improved. These results suggest that Nrf2 is a key factor inhibiting the differentiation of GSCs, and knockdown of Nrf2 may promote the differentiation process, providing a therapy target for GSCs.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Handong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Youwu
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Neurosurgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Yangchun
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Ji
authors.affiliation: Department of Neurosurgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Huandong
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008819:Mice, Nude; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism*; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D014407:Tumor Cells, Cultured
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human