title: Induction of apoptosis of leukemic cells by TRUE gene silencing using small guide RNAs targeting the WT1 mRNA.
abstract: TRUE gene silencing is a technology to eliminate specific cellular RNAs by using tRNase Z(L) and small guide RNA (sgRNA). Here we investigated how WT1-mRNA-targeting sgRNAs affect leukemic cells. We showed that sgRNA can be easily taken up by cells without any transfection reagents, and that the naked sgRNAs targeting the WT1 mRNA can reduce its mRNA levels and WT1 protein amounts in the WT1-expressing leukemic cells. Concomitantly, these sgRNAs efficiently induced apoptosis in these cells but not in WT1-nonexpressing cells. We also demonstrated that the reduction in the WT1 mRNA level is caused by its cleavage by tRNase Z(L).
authors: Laboratory of Hematology and Oncology, Graduate School of Health Sciences, Niigata University, 746-2 Asahimachi-dori, Chuo-ku, Niigata 951-8518, Japan.
authors: Norihiro
authors: N
authors: Watanabe
authors: Miwako
authors: M
authors: Narita
authors: Akie
authors: A
authors: Yamahira
authors: Tomoyo
authors: T
authors: Taniguchi
authors: Tatsuo
authors: T
authors: Furukawa
authors: Tetsuo
authors: T
authors: Yoshida
authors: Tatsuya
authors: T
authors: Miyazawa
authors: Masayuki
authors: M
authors: Nashimoto
authors: Masuhiro
authors: M
authors: Takahashi
mesh_terms: D017209:Apoptosis; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D020298:U937 Cells; D025721:WT1 Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D025721:WT1 Proteins; D004722:Endoribonucleases; C531011:tRNase Z, human