title: RNA interference targeting NRP-1 inhibits human glioma cell proliferation and enhances cell apoptosis.
abstract: Neuropilin-1 (NRP-1) is a non-tyrosine kinase receptor for vascular endothelial growth factor (VEGF) that was recently found to play a role in tumor functions. Previous studies demonstrated that NRP-1 was overexpressed in a number of human tumors, including glioblastoma (GBM). However, the role of NRP-1 in glioma progression has yet to be adequately elucidated. Thus, we examined the expression of NRP-1 in human glioma cell lines using Western blotting, and cell cycle distribution and proliferation by transfection of the U373 cell line with NRP-1 short interference RNA (siRNA). Results showed NRP-1 siRNA to significantly reduce NRP-1 gene expression, decrease in vitro cell proliferation and induce cell apoptosis in cultured glioma cells, along with the accumulation of cells in the G1 phase and a decrease in cells in the S phase. Our results further revealed that NRP-1 knockdown decreased the expression levels of Bcl-2 family proteins and deactivated extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) signaling pathways, closely associated with cancer progression. Thus, our results provide a molecular mechanism for the effect of NRP-1 in tumors, rendering NRP-1 an attractive candidate as a therapeutic target in certain types of cancer, such as GBM.
authors.affiliation: Department of Geriatrics, Huashan Hospital, Fudan University, Shanghai 200040, PR China.
authors.forename: Xiangyun
authors.initials: X
authors.lastname: Li
authors.forename: Ting
authors.initials: T
authors.lastname: Tang
authors.forename: Xiaozhe
authors.initials: X
authors.lastname: Lu
authors.forename: Houguang
authors.initials: H
authors.lastname: Zhou
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Huang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D039942:Neuropilin-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism / Q000494:pharmacology*; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D039942:Neuropilin-1; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases