title: RNAi-mediated inhibition of presenilin 2 inhibits glioma cell growth and invasion and is involved in the regulation of Nrg1/ErbB signaling.
abstract: Gliomas are the leading cause of death among adults with primary brain malignancies. Treatment for malignant gliomas remains limited, and targeted therapies have been incompletely explored. In this study, we found that the protein expression of presenilin 2 (PS2) was significantly increased in glioma tissues, at least partially because of promoter demethylation. We further evaluated the biological functions of PS2 in U251 glioma cell proliferation, migration, invasion, and tumor growth in vivo by specific inhibition of PS2 using short hairpin RNA (shRNA). We found that PS2 depletion inhibited glioma cell growth as the result of inhibited proliferation and induced apoptosis. PS2 depletion also decreased the invasive capability of glioma cells and anchorage-independent colony formation in soft agar. Moreover, suppression of PS2 expression significantly impaired the growth of glioma xenografts in nude mice. Finally, the decrease in glioma cell growth caused by PS2 depletion seems to involve Nrg1/ErbB signaling. In summary, our data highlight the use of RNA interference (RNAi) as a tool to better understand the molecular basis of PS2 in glioma progression and to uncover new targets for the treatment of glioma.
authors: Department of Neurosurgery and Institute for Functional Brain Disorders, Tangdu Hospital, Xi’an, People’s Republic of China.
authors: Bei
authors: B
authors: Liu
authors: Liang
authors: L
authors: Wang
authors: Liang-Liang
authors: LL
authors: Shen
authors: Ming-Zhi
authors: MZ
authors: Shen
authors: Xiao-Dong
authors: XD
authors: Guo
authors: Tao
authors: T
authors: Wang
authors: Qin-Chuan
authors: QC
authors: Liang
authors: Chao
authors: C
authors: Wang
authors: Jun
authors: J
authors: Zheng
authors: Yi
authors: Y
authors: Li
authors: Lin-Tao
authors: LT
authors: Jia
authors: Hua
authors: H
authors: Zhang
authors: Guo-Dong
authors: GD
authors: Gao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D020890:Neuregulin-1 / Q000378:metabolism; D016133:Polymerase Chain Reaction; D053766:Presenilin-2 / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
chemical_list: D020890:Neuregulin-1; D053766:Presenilin-2; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; C508861:PSEN2 protein, human