Chinese Bulletin of Life Sciences. The new therapy method of cancer sirna. HU Hai-Yan, ZHANG Yuan*

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1 Chinese Bulletin of Life Sciences Vol. 17, No. 3 Jun., (2005) sirna sirna(short interference RNA, sirna) 21~23nt RNA mrna sirna RNA RNA R730.59; Q813 A The new therapy method of cancer sirna HU Hai-Yan, ZHANG Yuan* (Institute of Hamatology, Medical College, Jinan University, Guangzhou , China) Abstract: sirna consists of double-stranded RNA of 21~23 nt, which can induce special mrna degradation. The special gene was interfered by posttranscriptional gene silencing. This paper summarizes the situation of sirna used in the therapy of carcinoma. Key words: posttranscriptional gene silencing; RNA interference; sirna; gene therapy DNA sirna ( ) [1] DNA (transcriptional gene silencing TGS); RNA (posttranscriptional gene silencing PTGS) RNA (RNA interference RNAi) PTGS Fire [2] RNA(double strands dsrna) No (1976 ) (1948 ) *

2 272 RNAi dsrna mrna RNA PTGS 21~23nt RNA sirna(short interference RNA sirna) [1] DNA sirna sirna [3~5] sirna 3' 2~3nt UU AA CC GG [6] RNA III sirna sirna II RNA III 3~5 T 3' 1~4 U sirna RNAi RNA PTGS mrna RNAi sirna [7] : PCR PCR sirna mrna PCR sirna mrna mrna RNA RNA (RDRP) mrna III Dicer mrna sirna Dicer dsrna sirna RNA (RNA induce silencing complex RISC) sirna mrna mrna 5' sirna mrna [8] sirna nt RNAi [9] AUG 100~200bp 3' sirna RNAi [10] sirna sirna Ambion QIAGEN ( misc/sirna finder.html (1) mrna AA 21~23nt 75nt (2)G C 50% (3) GGG sirna RNAi (4) BLAST 21~23nt sirna RNA sirna( sirna) sirna 29nt DNA (21nt sirna T7 5' 8nt) sirna sirna RNA III RNA DNA RNA sirna sirna RNAi [11] SBMA sirna 1 sirna 20 70

3 sirna 273 DNA 1.1 DNA CpG [12] CpG [13] CpG DNMT(DNA ) PCNA DNA CpG GSTP1 P16 E- CpG MBD(CpG ) CpG MBD MeCP2 DNA 5m CpG Sin3a HDAC HDACs MBD3 Mi-2NuRD MBD GSTP1 Mi-2NuRD -DNA 85% 30% 90% CpG Bakker [14] MBD2 MeCP2 HeP3 RT-PCR MBD2 MeCP2 sirna MBD2 MeCP2 CpG 1.2 t(8:21)(q22:q22) AML1/MTG8 10%~15% 21 AML1 (RUNX1) 8 MTG8 (ETO CBF 2T1) [15] AML1/ MTG8 MTG8 N-Cor msin3 Smad3 CAAT [16~17] Heidenreich [18] AML1/MTG8 sirna Kasumi-1 SKON 5' Cy3 sirna 16 sirna RT-PCR AML1/MTG8 mrna 50%~80% ( ) 5 AML mrna sirna sirna sirna TGFβ VitD3 CD11b CD14 sirna CD11b 5%~20% CD14 90% AML1/ MTG8 sirna AML1/MTG8 C/EBFα 15~20, 60 90% M-CSF-R 40% CD11b CD14 AML1/ MTG8 sirna (CML) c-abl 9 22 bcr-abl 210kD (p210) p210 CML CML bcr-abl CML bcr-abl p210 (FDA) Gleevec TM (STI 571) bcr-abl ATP bcr/abl Wohlbold [19] Scherr [20] bcr-abl sirna K562 BCR-ABL bcr/abl 2 DNA sirna DNA DNA DNA C (PKC) PKC (PKCδCF) DNA (DNA-PKcs) DNA p53 DNA [21]

4 274 DNA-PK PKCδCF c-abl PKCδCF DNA sprad1 sprad9 sphusl PKC Rad9 BH3 Bcl-2 Bcl-xL Bcl-2 Yoshida [22] PKCδ sirna 293T PKCδ mrna Rad9 Bcl-2 DNA 50% G 2 sirna PKCδ DNA 53BP1 Rad51 4 (HDAC4) HDAC4 HDAC Kao [23] HDAC4 sirna HDAC4 53BP1 G 2 DNA ATM ATR PKC sirna Collis [24] sirna 90% 1/4-3 Wortmannin DNA-PKcs LY ATR sirna MMS DNA Cdc25A DNA UV/IR Camptothecin Doxorubicin S/G Cdc25A Xiao [25] sirna Chk1 Cdc25A Cdc25A Cdk1/Cdk2 G 2 3 sirna EZH2 EZH2 EZH2 [26] EZH2 Zeste PcG SET EZH2 SET EZH2 pcdna3 ALPL WASF1 RAC3 CA6 SET EZH2 Graff [27] EZH2 sirna RWPE PL3 48 EZH2 mrna 60% % G 2 /M Gramil [28] DNA 400 Bax -1(Bax inhibitor-1, BI-1) BI-1 PC- 3 LNCaP Du-145 BI-1 sirna BI-1 BI-1 RNAi Bcl-2 BAG-1 Bcl-2 Takahashi [29] sirna Hela ERK1/2 1(MCL1) Bcl-2 Bcl-2 fortilin MCL1 fortilin MCL1 Zhang [30] sirna fortilin MCL1 sirna MCL1 fortilin fortilin MCL1 p53

5 sirna 275 p53 Shen [31] p53 sirna MCF-7 A549 16(HPV16) E6 E7 Leirdal [32] p53 sirna HepG2C S Trotta [33] BCR/ABL p53 p53 mdm2 bcr/abl + mdm2 La mdm2 mrna 5'UTR La sirna mdm2 La ErbB3 ErbB3 ErbB MAPK (MM) 12% MM IFNα CR IL-6 MM KAS-6/1 DP-6 IFNα IFNα MAP KAS-6/1 ANBL-6 IFNα ErbB3 Walters [34] ErbB3 sirna KAS-6/1 24 Westernblot ErbB3 IFN INFα IL-6 MAPK STAT ErbB3 IFNα MAPK STAT-3 4 sirna 1(TSP1) (VEGF) TSP1 Filleur [35] VEGF sirna VEGF TSP1 VEGF VEGF VEGF Ras-GAP PKC SPK Raf Ras (GEFs) Ras GEFs TCR PKC RasGTP (Ras-GAP) PKC COS Ras- GTP [36] EDG S1P PDGF BFGF TNF SPK S1P RasGEF SPK ERK [37] T24 24 VEGF 20 S1P Ras-GTP Shu [38] SPK1, 2 sirna T24 SPK1 sirna VEGF T24 Ras- GTP( ) ERK (Westernblot ) SPK2 sirna Mayerle [39] Westernblot 32 p120 Cadherin/Catenin p (P<0.05) sirna p120 40%

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