• 第三軍醫(yī)大學(xué)西南醫(yī)院普通外科（重慶400038）;

【摘要】目的 探討RNA干擾(RNA interference， RNAi)技術(shù)在大腸癌基因治療研究中的應(yīng)用。
方法 復(fù)習(xí)近幾年的相關(guān)文獻(xiàn)并進(jìn)行綜述。
結(jié)果 RNAi能夠高效特異地沉默同源基因表達(dá)，可在大腸癌發(fā)生、發(fā)展多個(gè)環(huán)節(jié)發(fā)揮重要作用。
結(jié)論 RNAi技術(shù)為大腸癌基因治療研究開(kāi)辟了新的途徑。

引用本文： 呂偉,張超. RNAi 在大腸癌基因治療中的應(yīng)用策略和展望. 中國(guó)普外基礎(chǔ)與臨床雜志, 2005, 12(6): 637-640. doi: 復(fù)制

1. Kerr D. Clinical development of gene therapy for colorectal cancer [J]. Nat Rev Cancer, 2003; 3(8)615.
2. Fire A, Xu S, Montgomery MK, et al. Potent and specific genetic interference by doublestranded RNA in Caenorhabditis elegans [J]. Nature， 1998; 391(6669)806.
3. Zamore PD. RNA interference: listening to the sound of silence [J]. Nat Struct Biol， 2001; 8(9)746.
4. Hammond SM, Bernstein E, Beach D, et al. An RNAdirected nuclease mediates posttranscriptional gene silencing in Drosophila cells [J]. Nature， 2000; 404(6775)293.
5. Bernstein E, Caudy AA, Hammond SM, et al. Role for a bidentate ribonuclease in the initiation step of RNA interference [J]. Nature， 2001; 409(6818)363.
6. Yang D, Lu H, Erickson JW. Evidence that processed small dsRNAs may mediate sequencespecific mRNA degradation during RNAi in Drosophila embryos [J]. Curr Biol， 2000; 10(19)1191.
7. Kawasaki H, Taira K. Short hairpin type of dsRNAs that are controlled by tRNA(Val) promoter significantly induce RNAimediated gene silencing in the cytoplasm of human cells [J]. Nucleic Acids Res， 2003; 31(2)700.
8. Caplen NJ, Fleenor J, Fire A, et al. dsRNAmediated gene silencing in cultured Drosophila cells: a tissue culture model for the analysis of RNA interference [J]. Gene， 2000; 252(1-2)95.
9. Zamore PD, Tuschl T, Sharp PA, et al. RNAi: doublestranded RNA directs the ATPdependent cleavage of mRNA at 21 to 23 nucleotide intervals [J]. Cell， 2000; 101(1)25.
10. Shen WG. RNA interference and its current application in mammals [J]. Chin Med J (Engl)， 2004; 117(7)1084.
11. Paul CP, Good PD, Winer I, et al. Effective expression of small interfering RNA in human cells [J]. Nat Biotechnol， 2002; 20(5)505.
12. Finkelstein SD, Przygodzki R, Pricolo VE, et al. Prediction of Biologic Aggressiveness in Colorectal Cancer by p53/Kras2 Topographic Genotyping [J]. Mol Diagn， 1996; 1(1)5.
13. Martinez LA, Naguibneva I, Lehrmann H, et al. Synthetic small inhibiting RNAs: efficient tools to inactivate oncogenic mutations and restore p53 pathways [J]. Proc Natl Acad Sci USA， 2002; 99(23)14849.
14. Yin JQ, Gao J, Shao R, et al. siRNA agents inhibit oncogene expression and attenuate human tumor cell growth [J]. J Exp Ther Oncol， 2003; 3(4)194.
15. Takeda A, Shimada H, Imaseki H, et al. Clinical significance of serum vascular endothelial growth factor in colorectal cancer patients: correlation with clinicopathological factors and tumor markers [J]. Oncol Rep， 2000; 7(2)333.
16. Takei Y, Kadomatsu K, Yuzawa Y, et al. A small interfering RNA targeting vascular endothelial growth factor as cancer therapeutics [J]. Cancer Res， 2004; 64(10)3365.
17. Nagy P, ArndtJovin DJ, Jovin TM. Small interfering RNAs suppress the expression of endogenous and GFPfused epidermal growth factor receptor (erbB1) and induce apoptosis in erbB1overexpressing cells [J]. Exp Cell Res， 2003; 285(1)39.
18. Zhang L, Yang N, MohamedHadley A, et al. Vectorbased RNAi, a novel tool for isoformspecific knockdown of VEGF and antiangiogenesis gene therapy of cancer [J]. Biochem Biophys Res Commun， 2003; 303(4)1169.
19. Nieth C, Priebsch A, Stege A, et al. Modulation of the classical multidrug resistance (MDR) phenotype by RNA interference (RNAi) [J]. FEBS Lett， 2003; 545(2-3)144.
20. Lum L, Yao S, Mozer B, et al. Identification of Hedgehog pathway components by RNAi in Drosophila cultured cells [J]. Science， 2003; 299(5615)2039.
21. Verma UN, Surabhi RM, Schmaltieg A, et al. Small interfering RNAs directed against betacatenin inhibit the in vitro and in vivo growth of colon cancer cells [J]. Clin Cancer Res， 2003; 9(4)1291.
22. 方向明，于皆平，羅和生. 大腸癌hTERT和P16表達(dá)與端粒酶活性的在系 [J]. 世界華人消化雜志， 2002； 10（1）12.
23. Horikawa I, Cable PL, Mazur SJ, et al. Downstream Eboxmediated regulation of the human telomerase reverse transcriptase (hTERT) gene transcription: evidence for an endogenous mechanism of transcriptional repression [J]. Mol Biol Cell， 2002; 13(8)2585.
24. Nephew KP, Huang TH. Epigenetic gene silencing in cancer initiation and progression [J]. Cancer Lett， 2003; 190(2)125.
25. Matsukura S, Jones PA, Takai D. Establishment of conditional vectors for hairpin siRNA knockdowns [J]. Nucleic Acids Res， 2003; 31(15)e77.
  1. 1. Kerr D. Clinical development of gene therapy for colorectal cancer [J]. Nat Rev Cancer, 2003; 3(8)615.
  2. 2. Fire A, Xu S, Montgomery MK, et al. Potent and specific genetic interference by doublestranded RNA in Caenorhabditis elegans [J]. Nature， 1998; 391(6669)806.
  3. 3. Zamore PD. RNA interference: listening to the sound of silence [J]. Nat Struct Biol， 2001; 8(9)746.
  4. 4. Hammond SM, Bernstein E, Beach D, et al. An RNAdirected nuclease mediates posttranscriptional gene silencing in Drosophila cells [J]. Nature， 2000; 404(6775)293.
  5. 5. Bernstein E, Caudy AA, Hammond SM, et al. Role for a bidentate ribonuclease in the initiation step of RNA interference [J]. Nature， 2001; 409(6818)363.
  6. 6. Yang D, Lu H, Erickson JW. Evidence that processed small dsRNAs may mediate sequencespecific mRNA degradation during RNAi in Drosophila embryos [J]. Curr Biol， 2000; 10(19)1191.
  7. 7. Kawasaki H, Taira K. Short hairpin type of dsRNAs that are controlled by tRNA(Val) promoter significantly induce RNAimediated gene silencing in the cytoplasm of human cells [J]. Nucleic Acids Res， 2003; 31(2)700.
  8. 8. Caplen NJ, Fleenor J, Fire A, et al. dsRNAmediated gene silencing in cultured Drosophila cells: a tissue culture model for the analysis of RNA interference [J]. Gene， 2000; 252(1-2)95.
  9. 9. Zamore PD, Tuschl T, Sharp PA, et al. RNAi: doublestranded RNA directs the ATPdependent cleavage of mRNA at 21 to 23 nucleotide intervals [J]. Cell， 2000; 101(1)25.
  10. 10. Shen WG. RNA interference and its current application in mammals [J]. Chin Med J (Engl)， 2004; 117(7)1084.
  11. 11. Paul CP, Good PD, Winer I, et al. Effective expression of small interfering RNA in human cells [J]. Nat Biotechnol， 2002; 20(5)505.
  12. 12. Finkelstein SD, Przygodzki R, Pricolo VE, et al. Prediction of Biologic Aggressiveness in Colorectal Cancer by p53/Kras2 Topographic Genotyping [J]. Mol Diagn， 1996; 1(1)5.
  13. 13. Martinez LA, Naguibneva I, Lehrmann H, et al. Synthetic small inhibiting RNAs: efficient tools to inactivate oncogenic mutations and restore p53 pathways [J]. Proc Natl Acad Sci USA， 2002; 99(23)14849.
  14. 14. Yin JQ, Gao J, Shao R, et al. siRNA agents inhibit oncogene expression and attenuate human tumor cell growth [J]. J Exp Ther Oncol， 2003; 3(4)194.
  15. 15. Takeda A, Shimada H, Imaseki H, et al. Clinical significance of serum vascular endothelial growth factor in colorectal cancer patients: correlation with clinicopathological factors and tumor markers [J]. Oncol Rep， 2000; 7(2)333.
  16. 16. Takei Y, Kadomatsu K, Yuzawa Y, et al. A small interfering RNA targeting vascular endothelial growth factor as cancer therapeutics [J]. Cancer Res， 2004; 64(10)3365.
  17. 17. Nagy P, ArndtJovin DJ, Jovin TM. Small interfering RNAs suppress the expression of endogenous and GFPfused epidermal growth factor receptor (erbB1) and induce apoptosis in erbB1overexpressing cells [J]. Exp Cell Res， 2003; 285(1)39.
  18. 18. Zhang L, Yang N, MohamedHadley A, et al. Vectorbased RNAi, a novel tool for isoformspecific knockdown of VEGF and antiangiogenesis gene therapy of cancer [J]. Biochem Biophys Res Commun， 2003; 303(4)1169.
  19. 19. Nieth C, Priebsch A, Stege A, et al. Modulation of the classical multidrug resistance (MDR) phenotype by RNA interference (RNAi) [J]. FEBS Lett， 2003; 545(2-3)144.
  20. 20. Lum L, Yao S, Mozer B, et al. Identification of Hedgehog pathway components by RNAi in Drosophila cultured cells [J]. Science， 2003; 299(5615)2039.
  21. 21. Verma UN, Surabhi RM, Schmaltieg A, et al. Small interfering RNAs directed against betacatenin inhibit the in vitro and in vivo growth of colon cancer cells [J]. Clin Cancer Res， 2003; 9(4)1291.
  22. 22. 方向明，于皆平，羅和生. 大腸癌hTERT和P16表達(dá)與端粒酶活性的在系 [J]. 世界華人消化雜志， 2002； 10（1）12.
  23. 23. Horikawa I, Cable PL, Mazur SJ, et al. Downstream Eboxmediated regulation of the human telomerase reverse transcriptase (hTERT) gene transcription: evidence for an endogenous mechanism of transcriptional repression [J]. Mol Biol Cell， 2002; 13(8)2585.
  24. 24. Nephew KP, Huang TH. Epigenetic gene silencing in cancer initiation and progression [J]. Cancer Lett， 2003; 190(2)125.
  25. 25. Matsukura S, Jones PA, Takai D. Establishment of conditional vectors for hairpin siRNA knockdowns [J]. Nucleic Acids Res， 2003; 31(15)e77.