title: Expression of R132H mutational IDH1 in human U87 glioblastoma cells affects the SREBP1a pathway and induces cellular proliferation.
abstract: Sterol regulatory element-binding protein-1a (SREBP1a) is a member of the SREBP family of transcription factors, which mainly controls homeostasis of lipids. SREBP1a can also activate the transcription of isocitrate dehydrogenase 1 (IDH1) by binding to its promoter region. IDH1 mutations, especially R132H mutation of IDH1, are a common feature of a major subset of human gliomas. There are few data available on the relationship between mutational IDH1 expression and SREBP1a pathway. In this study, we investigated cellular effects and SREBP1a pathway alterations caused by R132H mutational IDH1 expression in U87 cells. Two glioma cell lines, stably expressing mutational (U87/R132H) or wild type (U87/wt) IDH1, were established. A cell line, stably transfected with pcDNA3.1(+) (U87/vector), was generated as a control. Click-iT EdU assay, sulforhodamine B assay, and wound healing assay respectively showed that the expression of R132H induced cellular proliferation, cell growth, and cell migration. Western blot revealed that SREBP1 was increased in U87/R132H compared with that in U87/wt. Elevated SREBP1a and several its target genes, but not SREBP1c, were detected by real-time polymerase chain reaction in U87/R132H. All these findings indicated that R132H mutational IDH1 is involved in the regulation of proliferation, growth, and migration of glioma cells. These effects may partially be mediated by SREBP1a pathway.
authors.affiliation: Department of Neurosurgery, The Fourth Affiliated Hospital of Nantong University (The First People's Hospital of Yancheng), Yancheng 224006 Jiangsu Province, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhu
authors.forename: Gang
authors.initials: G
authors.lastname: Cui
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.forename: Qinian
authors.initials: Q
authors.lastname: Xu
authors.forename: Xiuyun
authors.initials: X
authors.lastname: Wang
authors.forename: Dai
authors.initials: D
authors.lastname: Zhou
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Lv
authors.forename: Linshan
authors.initials: L
authors.lastname: Fu
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.forename: Jianling
authors.initials: J
authors.lastname: Zuo
mesh_terms: D049108:Cell Enlargement; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D020125:Mutation, Missense; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human