title: siRNA targeting LMP1-induced apoptosis in EBV-positive lymphoma cells is associated with inhibition of telomerase activity and expression.
abstract: Epstein-Barr Virus (EBV) is closely associated with B cell malignancies. However, whether EBV appears to be absolutely required for cell proliferation and survival in lymphoma cells is still unknown. In this study, small interfering RNA (siRNA) targeting LMP1 was employed to investigate the effect of LMP1 on cell proliferation in EBV-positive lymphoblastoid B-cell line. A plasmid stable encoding 21-nt small RNA specifically and efficiently interfering LMP1 was constructed, resulting in a substantial loss of LMP1 mRNA and a significantly decreased LMP1 protein expression. Our data demonstrated that cell proliferation was completely inhibited and apoptosis was induced after knockdown of LMP1 gene in lymphoblastoid B-cell line. Also, we found that suppression of LMP1 caused downregulation of telomerase protein expression and decreased telomerase activity in lymphoma cells. In EBV-negative NPC cell line, transfection of plasmid expressing LMP1 greatly enhanced telomerase protein expression. Our results suggested that siRNA targeting LMP1 can induce apoptosis in EBV-positive lymphoma cells and is associated with inhibition of telomerase activity and expression. siRNA-directed LMP1 silencing may be of the therapeutic value for preventing and treating those EBV-associated tumors.
authors.affiliation: Department of Experimental Research, State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, 651 DongFeng Road East, GuangZhou 510060, China.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Mei
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Zhu
authors.forename: Jun-Min
authors.initials: JM
authors.lastname: Zhou
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.forename: Rong
authors.initials: R
authors.lastname: Deng
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
mesh_terms: D000818:Animals; D017209:Apoptosis; D002144:Callithrix; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004249:DNA Damage; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D008223:Lymphoma / Q000473:pathology / Q000628:therapy* / Q000821:virology*; D010957:Plasmids; D034741:RNA, Small Interfering / Q000494:pharmacology*; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014763:Viral Matrix Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D034741:RNA, Small Interfering; D014763:Viral Matrix Proteins; D019098:Telomerase