title: RNA interference-mediated silencing of iASPP induces cell proliferation inhibition and G0/G1 cell cycle arrest in U251 human glioblastoma cells.
abstract: iASPP is an evolutionally conserved inhibitory member of the ASPP (apoptosis-stimulating protein of p53) protein family. Overexpression of iASPP was observed in several types of human tumors, however, its role in tumorigenesis has not been fully clarified. To investigate the role of iASPP in human glioblastoma multiforme (GMB) progression, the authors employed lentivirus-mediated shRNA to silence endogenous iASPP expression and elucidated iASPP function by analysis of viability, colony formation, DNA synthesis, and cell cycle in p53-mutant glioblastoma cell line U251. iASPP was significantly and sustainably knocked down by iASPP-specific shRNA in U251 cells. Stable down-regulation of iASPP expression-induced cell proliferation inhibition and G0/G1 cell cycle arrest by down-regulation of cyclin D1 and up-regulation of p21(Waf1/Cip1). Thus, the findings not only provide a molecular basis for the role of iASPP in cell cycle progression of glioblastoma cells but also suggest a novel therapeutic target for the treatment of GBM.
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
authors.forename: Guilin
authors.initials: G
authors.lastname: Li
authors.forename: Renzhi
authors.initials: R
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Gao
authors.forename: Kan
authors.initials: K
authors.lastname: Deng
authors.forename: Junji
authors.initials: J
authors.lastname: Wei
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wei
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D016193:G1 Phase / Q000235:genetics / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018816:Genes, cdc / Q000187:drug effects; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D034622:RNA Interference / Q000502:physiology*; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C119612:PPP1R13L protein, human; D012097:Repressor Proteins