title: Knock-down of argonaute 2 (AGO2) induces apoptosis in myeloid leukaemia cells and inhibits siRNA-mediated silencing of transfected oncogenes in HEK-293 cells.
abstract: Understanding the role of oncomirs allows new insights into the development of modern therapeutic approaches for the repression of multiple oncomirs in cancer cells. At present, no suitable approach is available to repress the development of multiple oncomirs in cancer cells. Herein, we report that argonaute 2 (AGO2) could be a unique molecule to regulate the development of multiple oncomirs in cancer cells. Knock-down of AGO2 by custom-made AGO2 siRNA resulted in the induction of apoptosis in myeloid leukaemia cells (HL-60). Further investigations revealed that knock-down of AGO2 by custom-made AGO2 siRNA in HEK-293 cells resulted in silencing of the expression of target genes vascular endothelial growth factor A and histone deacetylase 2, which are known to be involved in the development of myeloid leukaemia. From these results, it can be predicted that AGO2 could regulate siRNA-mediated RNAi pathways in cancer cells. Furthermore, we investigated the possible implication of AGO2 in drug-induced apoptosis. Investigations revealed that treatment with the newly synthesized drug analogue SH-03[{(7S,7aR,13aS)-9,10-dimethoxy-3,3-dimethyl-7,7a,13,13atetrahydro-3H-chromeno[3,4-b]pyrano[2,3-h]chromen-7-ol}] could induce AGO2-mediated apoptosis in myeloid leukaemia cells via intrinsic apoptotic pathways independent of Dicer.
authors.affiliation: Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul, South Korea.
authors.forename: Pravin K
authors.initials: PK
authors.lastname: Naoghare
authors.forename: Yu Kyung
authors.initials: YK
authors.lastname: Tak
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Kim
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Han
authors.forename: Joon Myong
authors.initials: JM
authors.lastname: Song
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D060565:Argonaute Proteins / Q000235:genetics* / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D057809:HEK293 Cells; D056464:Histone Deacetylase 2 / Q000235:genetics; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology*; D009857:Oncogenes; D034741:RNA, Small Interfering / Q000235:genetics*; D012402:Rotenone / Q000031:analogs & derivatives / Q000494:pharmacology; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: C569212:9,10-dimethoxy-3,3-dimethyl-7,7a,13,13atetrahydro-3H-chromeno(3,4-b)pyrano(2,3-h)chromen-7-ol; C466422:AGO2 protein, human; D000970:Antineoplastic Agents; D060565:Argonaute Proteins; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D012402:Rotenone; D056464:Histone Deacetylase 2