2010, Number 1
<< Back Next >>
Rev Invest Clin 2010; 62 (1)
RNA interference: Biogenesis molecular mechanisms and its applications in cervical cancer
Peralta-Zaragoza O, Bermúdez-Morales VH, Madrid-Marina V
Language: Spanish
References: 137
Page: 63-80
PDF size: 150.38 Kb.
ABSTRACT
RNAi (RNA interference) is a natural process by which eukaryotic
cells silence gene expression through small interference
RNAs (siRNA) which are complementary to messenger
RNA (mRNA). In this process, the siRNA that are 21-25 nucleotides
long and are known as microRNA (miRNA), either
associate with the RNA-induced silencing complex (RISC),
which targets and cleaves the complementary mRNAs by the
endonucleolytic pathway, or repress the translation. It is also
possible to silence exogenous gene expression during viral infections
by using DNA templates to transcribe siRNA with
properties that are identical to those of bioactive microRNA.
Persistent human papillomavirus (HPV) infection is the main
etiological agent during cervical cancer development and the
HPV E6 and E7 oncogenes, which induce cellular transformation
and immortalization, represent strategic targets to be
silenced with siRNA. In several
in vitro and
in vivo studies, it
has been demonstrated that the introduction of siRNA directed
against the E6 and E7 oncogenes in human tumoral cervical
cells transformed by HPV, leads to the efficient silencing
of HPV E6 and E7 oncogene expression, which induces the
accumulation of the products of the p53 and pRb tumor suppressor
genes and activates the mechanism of programmed
cell death by apoptosis; thus, the progression of the tumoral
growth process may be prevented. The goal of this review is to
analyze the microRNA biogenesis process in the silencing of
gene expression and to discuss the different protocols for the
use of siRNA as a potential gene therapy strategy for
the treatment of cervical cancer.
REFERENCES
Napoli C, Lemieux C, Jorgensen R. Introduction of a Chimeric Chalcone Synthase Gene into Petunia Results in Reversible Co-Suppression of Homologous Genes in trans. Plant Cell 1990; 2: 279-89.
Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 1998; 391: 806-11.
Doench JG, Petersen CP, Sharp PA. siRNAs can function as miRNAs. Genes Dev 2003; 17: 438-42.
Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science 2001; 294: 853-8.
Lau NC, Lim LP, Weinstein EG, Bartel DP. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 2001; 294: 858-62.
Lee RC, Ambros V. An extensive class of small RNAs in Caenorhabditis elegans. Science 2001; 294: 862-4.
Tijsterman M, Ketting RF, Plasterk RH. The genetics of RNA silencing. Annu Rev Genet 2002; 36: 489-519.
zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer. 2002; 2: 342-350.
Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999; 189: 12-19.
Bermúdez-Morales V, Peralta-Zaragoza O, Madrid-Marina V. Gene therapy with cytokines against cervical cancer. Revista Salud Pública de México 2005; 47: 458-68.
Zheng YF, Rao ZG, Zhang JR. Effects of anti-HPV16 E6-ribozyme on the proliferation and apoptosis of human cervical cancer cell line CaSKi. Di Yi Jun Yi Da Xue Xue Bao 2002; 22: 496-8.
Choo CK, Ling MT, Suen CK, Chan KW, Kwong YL. Retrovirusmediated delivery of HPV16 E7 antisense RNA inhibited tumorigenicity of CaSki cells. Gynecol Oncol 2000; 78: 293-301.
Storey A, Oates D, Banks L, Crawford L, Crook T. Anti-sense phosphorothioate oligonucleotides have both specific and nonspecific effects on cells containing human papillomavirus type 16. Nucleic Acids Res 1991; 19: 4109-14.
Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 2001; 411: 494-8.
Elbashir SM, Martinez J, Patkaniowska A, Lendeckel W, Tuschl T. Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. EMBO J 2001; 20: 6877-88.
Bartel PD. MicroRNAs: Genomics, Biogenesis, Mechanism, and Function. Cell 2004; 116: 281-97.
Johnson SM, Lin SY, Slack FJ. The time of appearance of the C. elegans let-7 microRNA is transcriptionally controlled utilizing a temporal regulatory element in its promoter. Dev Biol 2003; 259: 364.79.
Lagos-Quintana M, Rauhut R, Meyer J, Borkhardt A, Tuschl T (2003). New microRNAs from mouse and human. RNA 2003; 9: 175-9.
Denli AM, Tops BBJ, Plasterk RHA, Ketting RF, Hannon GJ. Processing of primary microRNAs by the Microprocessor complex. Nature 2004; 432: 231-5.
Gregory RI, Yan KP, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, Shiekhattar R. The Microprocessor complex mediates the genesis of microRNAs. Nature 2004; 432: 235-40.
Han J, Lee Y, Yeom KH, Kim YK, Jin H, Kim VN. The Drosha- DGCR8 complex in primary microRNA processing. Genes and Development. 2004; 18: 3016-27.
Landthaler M, Yalcin A, Tuschl T. The human DiGeorge syndrome critical region gene 8 and its D. melanogaster ho-molog are required for miRNA biogenesis. Current Biology. 2004; 14: 2162-7.
Cai X, Hagedorn CH, Cullen BR. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 2004; 10: 1957-66.
Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature 2003;425: 415-19.
Lee Y, Jeon K, Lee JT, Kim S, Kim VN. MicroRNA maturation: stepwise processing and subcellular localization. EMBO Journal 2002; 21: 4663-70.
Brownawell AM, Macara IG. Exportin-5, a novel karyo-pherin, mediates nuclear export of double-stranded RNA binding proteins. J Cell Biology 2002; 156: 53-64.
Yi R, Qin Y, Macara IG, Cullen BR. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes and Development 2003; 17: 3011-16.
Bohnsack MT, Czaplinski K, Gorlich D. Exportin 5 is a RanGTPdependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA 2004; 10: 185-91.
Lund E, Guttinger S, Calado A, Dahlberg JE, Kutay U. Nuclear export of microRNA precursors. Science 2004; 303: 95-8.
Knight SW, Bass BL. A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans. Science 2001; 293: 2269-71.
Ketting RF, Fischer SE, Bernstein E, Sijen T, Hannon GJ, Plasterk RH. Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev 2001; 15: 2654-9.
Bernstein E, Caudy AA, Hammond SM, Hannon GJ. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 2001; 409: 363-6.
33 . Provost P, Dishart D, Doucet J, Frendewey D, Samuelsson B, Radmark O. Ribonuclease activity and RNA binding of recombinant human Dicer. EMBO J 2002; 21: 5864-74.
Zhang H, Kolb FA, Brondani V, Billy E, Filipowicz W. Human Dicer preferentially cleaves dsRNAs at their termini without a requirement for ATP. EMBO J 2002; 21: 5875-85.
Hammond SM, Bernstein E, Beach D, Hannon GJ. An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells, Nature 2000; 404: 293-6.
Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell 2005; 123: 631-40.
Martinez J, Patkaniowska A, Urlaub H, Luhrmann R, Tuschl T. Single-stranded antisense siRNAs guide target RNA cleavage in RNAi, Cell 2002; 110: 563-74.
Nykanen A, Haley B, Zamore PD. ATP requirements and small interfering RNA structure in the RNA interference pathway, Cell 2001; 107: 309-21.
Hammond SM, Boettcher S, Caudy AA, Kobayashi R, Hannon GJ. Argonaute2, a link between genetic and biochemical analyses of RNAi. Science 2001; 293: 1146-50.
Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L, et al. miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs. Genes Dev 2000; 16: 720-8.
Hutvagner G, Zamore PD. A microRNA in a multiple-turnover RNAi enzyme complex. Science 2002; 297: 2056-60.
Pham JW, Pellino JL, Lee YS, Carthew RW, Sontheimer EJ. A Dicer- 2-dependent 80s complex cleaves targeted mRNAs during RNAi in Drosophila. Cell 2004; 117: 83-94.
Sontheimer EJ. Assembly and function of RNA silencing complexes, Nat Rev Mol Cell Biol 2005; 6: 127-38.
Filipowicz W. RNAi: the nuts and bolts of the RISC machine. Cell 2005; 122: 17-20.
Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM, Song JJ et al. Argonaute 2 is the catalytic engine of mammalian RNAi. Science 2004; 305: 1437-41.
Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, Tuschl T. Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell 2004; 15: 185-97.
Song JJ, Smith SK, Hannon GJ, Joshua-Tor L. Crystal structure of Argonaute and its implications for RISC slicer activity. Science 2004; 305: 1434-7.
Ma JB, Yuan YR, Meister G, Pei Y, Tuschl T, Patel DJ. Structural basis for 5'-end-specific recognition of guide RNA by the A. fulgidus Piwi protein, Nature 2005; 434: 666-70.
Rivas FV, Tolia NH, Song JJ, Aragon JP, Liu J, Hannon GJ, Joshua- Tor L. Purified Argonaute 2 and an siRNA form recombinant human RISC. Nat Struct Mol Biol 2005; 12: 340-9.
Haley B, Zamore PD. Kinetic analysis of the RNAi enzyme complex, Nat Struct Mol Biol 2004; 11: 599-606.
Okamura K, Ishizuka A, Siomi H, Siomi MC. Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways, Genes Dev 2004; 18: 1655-66.
Jiang F, Ye X, Liu X, Fincher L, McKearin D, Liu Q. Dicer-1 and R3D1-L catalyze microRNA maturation in Drosophila. Genes Dev 2005; 19: 1674-9.
Saito K, Ishizuka A, Siomi H, Siomi MC. Processing of pre-microRNAs by the Dicer-1-Loquacious complex in Drosophila cells. PLoS Biol 2005; 3: 1202-12.
Tabara H, Yigit E, Siomi H, Mello CC. The dsRNA binding protein RDE-4 interacts with RDE-1, DCR-1, and a DExH-box helicase to direct RNAi in C. elegans. Cell 2002; 109: 861-71.
Tahbaz N, Kolb FA, Zhang H, Jaronczyk K, Filipowicz W, Hobman TC. Characterization of the interactions between mammalian PAZ PIWI domain proteins and Dicer. EMBO Rep 2004; 5: 189-94.
Chendrimada TP, Gregory RI, Kumaraswamy E, Norman J, Cooch N, Nishikura K, Shiekhattar R. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature 2005; 436: 740-4.
Liu Q, Rand TA, Kalidas S, Du F, Kim HE, Smith DP, Wang X, R2D2, a bridge between the initiation and effector steps of the Drosophila RNAi pathway. Science 2003; 301: 1921-5.
Grishok A, Tabara H, Mello CC. Genetic requirements for inheritance of RNAi in C. elegans. Science 2000; 287: 2494-7.
59 Grishok A, Pasquinelli AE, Conte D, Li N, Parrish S, Ha I, et al. Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell 2001; 106: 23-34.
Tomari Y, Matranga C, Haley B, Martinez N, Zamore PD. A protein sensor for siRNA asymmetry. Science 2004; 306: 1377-80.
Zhang H, Kolb FA, Jaskiewicz L, Westhof E, Filipowicz W. Single processing center models for human Dicer and bacterial RNase III. Cell 2004; 118: 57-68.
Doi N, Zenno S, Ueda R, Ohki-Hamazaki H, Ui-Tei K, Saigo K. Short-interfering-RNA-mediated gene silencing in mammalian cells requires Dicer and eIF2C translation initiation factors. Curr Biol 2003; 13: 41-6.
Lee YS, Nakahara K, Pham JW, Kim K, He Z, Sontheimer EJ, Carthew RW. Distinct roles for Drosophila Dicer-1 and Dicer- 2 in the siRNA/miRNA silencing pathways. Cell 2004; 117: 69-81.
Ghildiyal M, Seitz H, Horwich MD, Li C, Du T, Lee S, et al. Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells. Science 2008; 320(5879): 1077-81.
Czech B, Malone CD, Zhou R, Stark A, Schlingeheyde C, Dus M, Perrimon N, et al. An endogenous small interfering RNA pathway in Drosophila. Nature 2008; 453(7196): 798-802.
Okamura K, Chung WJ, Ruby JG, Guo H, Bartel DP, Lai EC. The Drosophila hairpin RNA pathway generates endogenous short interfering RNAs. Nature 2008; 453(7196): 803-6.
Kawamura Y, Saito K, Kin T, Ono Y, Asai K, Sunohara T, Okada TN, Siomi MC, Siomi H. Drosophila endogenous small RNAs bind to Argonaute 2 in somatic cells. Nature 2008; 453(7196): 793-7.
Okamura K, Balla S, Martin R, Liu N, Lai EC. Two distinct mechanisms generate endogenous siRNAs from bidirectional transcription in Drosophila melanogaster. Nature Struct Mol Biol 2008; 15: 581-90.
Chung WJ, Okamura K, Martin R, Lai EC. Endogenous RNA interference provides a somatic defense against Drosophila transposons. Curr Biol 2008; 18: 795-802.
Tabara H, Sarkissian M, Kelly WG, Fleenor J, Grishok A, Timmons L, et al. The rde-1 gene, RNA interference, and transposon silencing in C. elegans. Cell 1999; 99(2): 123-32.
Ketting RF, Haverkamp TH, van Luenen HG, Plasterk RH. Mut-7 of C. elegans, required for transposon silencing and RNA interference, is a homolog of Werner syndrome helicase and RNaseD. Cell 1999: 99; 133-41.
Zhou R, Hotta I, Denli AM, Hong P, Perrimon N, Hannon GJ. Comparative analysis of argonaute-dependent small RNA pathways in Drosophila. Mol Cell 2008; 32(4): 592-99.
Förstemann K, Tomari Y, Du T, Vagin VV, Denli AM, Bratu DP, Klattenhoff C, Theurkauf WE, Zamore PD. Normal microRNA maturation and germ-line stem cell maintenance requires Loquacious, a double-stranded RNA-binding domain protein. PLoS Biol 2005; 3(7): 1187-201.
Yang N, Kazazian HHJ. L1 retrotransposition is suppressed by endogenously encoded small interfering RNAs in human cultured cells. Nature Struct Mol Bio 2006; 13: 763-71.
Tam OH, Aravin AA, Stein P, Girard A, Murchison EP, Cheloufi S, et al. Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature 2008; 453(7194): 534-8.
Watanabe T, Totoki Y, Toyoda A, Kaneda M, Kuramochi-Miyagawa S, Obata Y, et al. Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature 2008; 453(7194): 539-43.
Sasidharan R, Gerstein M. Genomics: protein fossils live on as RNA. Nature 2008; 453: 729-31.
Yoshinari K, Miyagishi M, Taira K. Effectson RNAi of the tight structure, sequence and position of the targeted region. Nucleic Acid Res 2004; 32: 691-9.
Khvorova A, Reynolds A, Jayasena SD. Functional siRNAs and miRNAs exhibit strand bias. Cell 2003; 115: 209-16.
Schwarz DS, Hutvágner G, Du T, Xu Z, Aronin N, Zamore PD. Asymmetry in the assembly of the RNAi enzyme complex. Cell 2003; 115: 199-208.
Reynolds A, Leake D, Boese Q, Scaringe S, Marshall WS, Khvorova A. Rational siRNA design for RNA interference. Nat Biotechnol 2004; 22: 326-30.
Ui-Tei K, Naito Y, Takahashi F, Haraguchi T, Ohki-Hamazaki H, Juni A, et al. Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference. Nucleic Acids Res 2004; 32: 936-48.
Sioud M, Sorensen DR. Cationic liposome-mediated delivery of siRNAs in adult mice. Biochem Biophys Res Commun 2003; 312: 1220-5.
Zhang X, Shan P, Jiang D, Noble PW, Abraham NG, Kappas A, Lee PJ. Small interfering RNA targeting heme oxygenase-1 enhances ischemia-reperfusion-induced lung apoptosis. J Biol Chem 2004; 279: 10677-84.
Liu C, Shi Y, Han Z, Pan Y, Liu N, Han S, et al. Suppression of the dual-specificity phosphatase MKP-1 enhances HIF-1 transactivation and increases expression of EPO. Biochem Biophys Res Commun 2003; 312: 780-6.
Brummelkamp TR, Bernards R, Agami R. A system for stable expression of short interfering RNAs in mammalian cells. Science 2002; 296: 550-3.
Sui G, Soohoo C, Affar el B, Gay F, Shi Y, Forrester WC, Shi Y. A DNA vector-based RNAi technology to suppress gene expression in mammalian cells. Proc Natl Acad Sci USA 2002; 99: 5515-20.
Pinkenburg O, Platz J, Beisswenger C, Vogelmeier C, Bals R. Inhibition of NF-kappaB mediated inflammation by siRNA expressed by recombinant adeno-associated virus. J Virol Meth 2004; 120: 119-22.
Sanchez-Vargas I, Travanty EA, Keene KM, Franz AW, Beaty BJ, Blair CD, Olson AE. RNA interference, arthropod-borne viruses, and mosquitoes. Virus Res 2004; 102: 65-74.
An DS, Xie Y, Mao SH, Morizono K, Kung SJ, Chen IS, Efficient lentiviral vectors for short hairpin RNA delivery into human cells. Hum Gene Ther 2003; 14: 1207-12.
Lee JS, Hmama Z, Mui A, Reiner NE. Stable gene silencing in human monocytic cell lines using lentiviral-delivered small interference RNA. Silencing of the p110alpha isoform of phosphoinositide 3-kinase reveals differential regulation of adherence induced by 1alpha, 25-dihydroxycholecalciferol and bacterial lipopolysaccharide. J Biol Chem 2004; 279: 9379-88.
Li MJ, Rossi JJ, Lentiviral vector delivery of recombinant small interfering RNA expression cassettes. Meth Enzymol 2005; 392: 218-26.
Futami T, Miyagishi M, Seki M, Taira K. Induction of apoptosis in HeLa cells with siRNA expression vector targeted against bcl- 2. Nucl Acids Res Suppl 2002; 2: 251-2.
Matsukura S, Jones PA, Takai D. Establishment of conditional vectors for hairpin siRNA knockdowns. Nucleic Acids Res. 2003; 31: 77-81.
van de Wetering M, Oving I, Muncan V, Pon Fong MT, Brantjes H, van Leenen D, Holstege FC, et al. Specific inhibition of gene expression using a stably integrated, inducible small-interfering- RNA vector. EMBO Rep 2003; 4: 609-15.
de Felipe P, Izquierdo M. Tricistronic and tetracistronic retroviral vectors for gene transfer. Hum Gene Ther 2000; 11: 1921-31.
Devroe E, Silver PA. Retrovirus-delivered siRNA. BMC Biotechnol. 2002; 2: 15-20.
Freytag SO, Khil M, Stricker H, Peabody J, Menon M, DePeralta- Venturina M, et al. Phase I study of replication-competent adenovirus-mediated double suicide gene therapy for the treatment of locally recurrent prostate cancer. Cancer Res 2002; 62: 4968-76.
Carette JE, Overmeer RM, Schagen FH, Alemany R, Barski OA, Gerritsen WR, Van Beusechem VW. Conditionally replicating adenoviruses expressing short hairpin RNAs silence the expression of a target gene in cancer cells. Cancer Res 2004; 64: 2663-7.
Hommel JD, Sears RM, Georgescu D, Simmons DL, DiLeone RJ. Local gene knockdown in the brain using viral-mediated RNA interference. Nat Med 2003; 9: 1539-44.
Van den Haute C, Eggermont K, Nuttin B, Debyser Z, Baekelandt V. Lentiviral vector-mediated delivery of short hairpin RNA results in persistent knockdown of gene expression in mouse brain. Hum Gene Ther 2003; 14: 1799-807.
Kjaer SK, van den Brule AJC, Paull G, Svare EI, Sherman ME, Thomsen BL, et al. Type specific persistence of high risk Human Papillomavirus (HPV) as indicator of high grade cervical squamous intreapithelial lesions in young women: population based prospective follow up study. BMJ 2002; 325: 1-7.
zur Hausen H. Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J Natl Cancer Inst 2000; 92(9): 690-8.
Wise-Draper TM, Wells SI. Papillomavirus E6 and E7 proteins and their cellular targets. Front Biosci 2008; 13: 1003-17.
Oren M. Decision making by p53: life, death and cancer. Cell Death Differ 2003; 10(4): 431-42.
Vousden KH, Lane DP. p53 in health and disease. Nat Rev Mol Cell Biol 2007; 8(4): 275-83.
Dick FA, Dyson NJ. Three regions of the pRb pocket domain affect its inactivation by human papillomavirus E7 proteins. J Virol 2002; 76: 6224-34.
Antinore MJ, Birrer MJ, Patel D, Nader L, McCance DJ. The human papillomavirus type 16 E7 gene product interacts with and trans-activates the AP1 family of transcription factors. EMBO J 1996; 15: 1950-60.
Veldman T, Liu X, Yuan H, Schlegel R. Human papillomavirus E6 and Myc proteins associate in vivo and bind to and cooperatively activate the telomerase reverse transcriptase promoter. Proc Natl Acad Sci USA 2003; 100: 8211-16.
Yukawa K, Butz K, Yasui T, Kikutani H, Hoppe-Seyler F. Regulation of human papillomavirus transcription by the differentiation- dependent epithelial factor Epoc-1/skn-1a. J Virol 1996; 70: 10-16.
Cho NH, Kim YT, Kim JW. Alteration of cell cycle in cervical tumor associated with human papillomavirus: cyclin-dependent kinase inhibitors. Yonsei Med J 2002; 436: 722-8.
Phillips AC, Vousden KH. Analysis of the interaction between human papillomavirus type 16 E7 and the TATA-binding protein, TBP. J Gen Virol 1997; 78: 905-9.
Maldonado E, Cabrejos ME, Banks L, Allende JE. Human papillomavirus- 16 E7 protein inhibits the DNA interaction of the TATA binding transcription factor. J Cell Biochem 2002; 85(4): 663-9.
Desaintes C, Hallez S, Van Alphen P, Burny A. Transcriptional activation of several heterologous promoters by the E6 protein of human papillomavirus type 16. J Virol 1992; 66: 325-33.
Nees M, Geoghegan JM, Hyman T, Frank S, Miller L, Woodworth CD. Papillomavirus type 16 oncogenes downregulate expression of interferon-responsive genes and upregulate proliferation-associated and NF-kappaB-responsive genes in cervical keratinocytes. J Virol 2001; 75: 4283-96.
Peralta-Zaragoza O, Bermúdez-Morales VH, Gutiérrez-Xicotencatl L, Alcocer-González JM, Recillas-Targa F, Madrid-Marina V. E6 and E7 oncoproteins from human papillomavirus type 16 induce activation of human transforming growth factor beta-1 promoter throughout Sp1 regulatory element. Viral Immunology 2006; 19: 468-80.
Halbert CL, Demers GW, Galloway DA. The E6 and E7 genes of human papillomavirus type 6 have weak immortalizing activity in human epithelial cells. J Virol 1992; 66: 2125-34.
Munger K, Howley PM. Human papillomavirus immortalization and transformation functions. Virus Res 2002; 89: 213-28.
Jiang M, Milner J. Selective silencing of viral gene expression in HPV-positive human cervical carcinoma cells treated with siRNA, a primer of RNA interference. Oncogene. 2002; 21: 6041-8.
Yoshinouchi M, Yamada T, Kizaki M, Fen J, Koseki T, Ikeda Y, et al. In vitro and in ivo Growth Suppression of Human Papillomavirus 16-Positive Cervical Cancer Cells by E6 siRNA. Molecular Therapy 2003; 8: 762-8.
Butz K, Ristriani T, Hengstermann A, Denk C, Scheffner M, Hoppe- Seyler F. siRNA targeting of the viral E6 oncogene efficiently kills human papillomavirus-positive cancer cells. Oncogene 2003; 22: 5938-45.
Lea JS, Sunaga N, Sato M, Kalahasti G, Miller DS, Minna JD, Muller CY. Silencing of HPV 18 oncoproteins With RNA interference causes growth inhibition of cervical cancer cells. Reprod Sci. 2007; 14: 20-28.
Butz K, Denk C, Ullmann A, Scheffner M, Hoppe-Seyler F. Induction of apoptosis in human papillomaviruspositive cancer cells by peptide aptamers targeting the viral E6 oncoprotein. Proc Natl Acad Sci USA 2000; 97: 6693-7.
Koivusalo R, Krausz E, Helenius H, Hietanen S. Chemotherapy compounds in cervical cancer cells primed by reconstitution of p53 function after short interfering RNA mediated degradation of human papillomavirus 18 E6 mRNA: Opposite effect of siRNA in combination with different drugs. Mol Pharmacol 2005; 68: 372-82.
Putral LN, Bywater MJ, Gu W, Saunders NA, Gabrielli BG, Leggatt GR, McMillan NA. RNA interference against human papillomavirus oncogenes in cervical cancer cells results in increased sensitivity to cisplatin. Mol Pharmacol 2005; 68: 1311-19.
Niu XY, Peng ZL, Duan WQ, Wang H, Wang P. Inhibition of HPV 16 E6 oncogene expression by RNA interference in vitro and in vivo. Int J Gynecol Cancer 2006; 16: 743-51.
Jiang M, Rubbi CP, Milner J. Gel-based application of siRNA to human epithelial cancer cells induces RNAi-dependent apoptosis. Oligonucleotides 2004; 14: 239-48.
Takuma F, Miyuki S, Eri I, Takahiro O, Yoshifumi T, Shigenori H, et al. Intratumor injection of small interfering RNA-targeting human papillomavirus 18 E6 and E7 successfully inhibits the growth of cervical cancer. Int J Oncology 2006; 29: 541-8.
Gu W, Putral L, McMillan N. siRNA and shRNA as anticancer agents in a cervical cancer model. Methods Mol Biol 2008; 442: 159-72.
Naldini L, Verma IM. Lentiviral vectors. Adv Virus Res 2000: 55; 599-609.
Wang R, Lin F, Wang X, Gao P, Dong K, Wei SH, et al. The therapeutic potential of survivin promoter-driven siRNA on suppressing tumor growth and enhancing radiosensitivity of human cervical carcinoma cells via downregulating hTERT gene expression. Cancer Biol Ther 2007; 6(8): 1295-301.
Zaffaroni N, Pennati M, Daidone MG. Survivin as a target for new anticancer interventions. J Cell Mol Med 2005; 9(2): 360-72.
Kuner R, Vogt M, Sultmann H, Buness A, Dymalla S, Bulkescher J, et al. Identification of cellular targets for the human papillomavirus E6 and E7 oncogenes by RNA interference and transcriptome analyses. J Mol Med. 2007; 85: 1253-62.
Naito Y, Yamada T, Ui-Tei K, Morishita S, Saigo K. siDirect: highly effective, target-specific siRNA design software for mammalian RNA interference. Nucleic Acids Res 2004; 32: 124-9.
Yamato K, Yamada T, Kizaki M, Ui-Tei K, Natori Y, Fujino M, et al. New highly potent and specific E6 and E7 siRNAs for treatment of HPV16 positive cervical cancer. Cancer Gene Therapy 2008; 15: 140-53.
http://www.ambion.com/techlib/misc/siRNA_finder.html.
Sima N, Wang W, Kong D, Deng D, Xu Q, Zhou J, et al. RNA interference against HPV16 E7 oncogene leads to viral E6 and E7 suppression in cervical cancer cells and apoptosis via upregulation of Rb and p53. Apoptosis 2008; 13: 273-81.