Skip to main content
SpringerLink
Log in

Noncoding RNA for Cancer Gene Therapy

  • Chapter
  • First Online:
Current Strategies in Cancer Gene Therapy

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 209))

Abstract

Gene therapy is a prospective strategy to modulate gene expression level in specific cells to treat human inherited diseases, cancers, and acquired disorders. A subset of noncoding RNAs, microRNAs (miRNAs) and small interference RNAs (siRNAs), compose an important class of widely used effectors for gene therapy, especially in cancer treatment. Functioning through the RNA interference (RNAi) mechanism, miRNA and siRNA show potent ability in silencing oncogenic factors for cancer gene therapy. For a better understanding of this field, we reviewed the mechanism and biological function, the principles of design and synthesis, and the delivery strategies of noncoding RNAs with clinical potentials in cancer gene therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

miRNA:

MicroRNA

siRNA:

Small interference RNA

RNAi:

RNA interference

Ago2:

Argonaute 2

RISC:

RNA-induced silencing complex

TRBP:

TAR-RNA binding protein

PACT:

Protein activator of PKR

shRNA:

Short hairpin RNA

TRC:

The RNAi Consortium

DOPC:

1,2-dioleoyl-sn-glycero-3-phosphatidylcholine

References

  • Cai X, Hagedorn CH, Cullen BR (2004) Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 10(12):1957–1966

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chan JA, Krichevsky AM, Kosik KS (2005) MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 65(14):6029–6033

    Article  CAS  PubMed  Google Scholar 

  • Cheng CJ, Bahal R, Babar IA et al (2015) MicroRNA silencing for cancer therapy targeted to the tumour microenvironment. Nature 518(7537):107–110

    Article  CAS  PubMed  Google Scholar 

  • Denli AM, Tops BB, Plasterk RH et al (2004) Processing of primary microRNAs by the Microprocessor complex. Nature 432(7014):231–235

    Article  CAS  PubMed  Google Scholar 

  • Du T, Zamore PD (2005) microPrimer: the biogenesis and function of microRNA. Development 132(21):4645–4652

    Article  CAS  PubMed  Google Scholar 

  • Elbashir SM, Harborth J, Lendeckel W et al (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411(6836):494–498

    Article  CAS  PubMed  Google Scholar 

  • Esquela-Kerscher A, Trang P, Wiggins JF et al (2008) The let-7 microRNA reduces tumor growth in mouse models of lung cancer. Cell Cycle 7(6):759–764

    Article  CAS  PubMed  Google Scholar 

  • Fire A, Xu S, Montgomery MK et al (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391(6669):806–811

    Article  CAS  PubMed  Google Scholar 

  • Gentner B, Schira G, Giustacchini A et al (2009) Stable knockdown of microRNA in vivo by lentiviral vectors. Nat Methods 6(1):63–66

    Article  CAS  PubMed  Google Scholar 

  • Gregory RI, Yan KP, Amuthan G et al (2004) The Microprocessor complex mediates the genesis of microRNAs. Nature 432(7014):235–240

    Article  CAS  PubMed  Google Scholar 

  • Gregory RI, Chendrimada TP, Cooch N et al (2005) Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell 123(4):631–640

    Article  CAS  PubMed  Google Scholar 

  • Gregory PA, Bert AG, Paterson EL et al (2008) The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol 10(5):593–601

    Article  CAS  PubMed  Google Scholar 

  • Grimm D, Streetz KL, Jopling CL et al (2006) Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature 441(7092):537–541

    Article  CAS  PubMed  Google Scholar 

  • Hornung V, Guenthner-Biller M, Bourquin C et al (2005) Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat Med 11(3):263–270

    Article  CAS  PubMed  Google Scholar 

  • Hu-Lieskovan S, Heidel JD, Bartlett DW et al (2005) Sequence-specific knockdown of EWS-FLI1 by targeted, nonviral delivery of small interfering RNA inhibits tumor growth in a murine model of metastatic Ewing’s sarcoma. Cancer Res 65(19):8984–8992

    Article  CAS  PubMed  Google Scholar 

  • Hutvagner G, McLachlan J, Pasquinelli AE et al (2001) A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science 293(5531):834–838

    Article  CAS  PubMed  Google Scholar 

  • Johnson CD, Esquela-Kerscher A, Stefani G et al (2007) The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res 67(16):7713–7722

    Article  CAS  PubMed  Google Scholar 

  • Judge AD, Sood V, Shaw JR et al (2005) Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA. Nat Biotechnol 23(4):457–462

    Article  CAS  PubMed  Google Scholar 

  • Judge AD, Bola G, Lee AC et al (2006) Design of noninflammatory synthetic siRNA mediating potent gene silencing in vivo. Mol Ther 13(3):494–505

    Article  CAS  PubMed  Google Scholar 

  • Ketting RF, Fischer SE, Bernstein E et al (2001) Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev 15(20):2654–2659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khan AA, Betel D, Miller ML et al (2009) Transfection of small RNAs globally perturbs gene regulation by endogenous microRNAs. Nat Biotechnol 27(6):549–555

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kim DH, Longo M, Han Y et al (2004) Interferon induction by siRNAs and ssRNAs synthesized by phage polymerase. Nat Biotechnol 22(3):321–325

    Article  CAS  PubMed  Google Scholar 

  • Kim DH, Behlke MA, Rose SD et al (2005) Synthetic dsRNA Dicer substrates enhance RNAi potency and efficacy. Nat Biotechnol 23(2):222–226

    Article  CAS  PubMed  Google Scholar 

  • Kota J, Chivukula RR, O’Donnell KA et al (2009) Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 137(6):1005–1017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krichevsky AM, Gabriely G (2009) miR-21: a small multi-faceted RNA. J Cell Mol Med 13(1):39–53

    Article  CAS  PubMed  Google Scholar 

  • Kumar MS, Erkeland SJ, Pester RE et al (2008) Suppression of non-small cell lung tumor development by the let-7 microRNA family. Proc Natl Acad Sci U S A 105(10):3903–3908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Landen CN Jr, Chavez-Reyes A, Bucana C et al (2005) Therapeutic EphA2 gene targeting in vivo using neutral liposomal small interfering RNA delivery. Cancer Res 65(15):6910–6918

    Article  CAS  PubMed  Google Scholar 

  • Lee Y, Ahn C, Han J et al (2003) The nuclear RNase III Drosha initiates microRNA processing. Nature 425(6956):415–419

    Article  CAS  PubMed  Google Scholar 

  • Lee Y, Kim M, Han J et al (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23(20):4051–4060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee CC, MacKay JA, Frechet JM et al (2005) Designing dendrimers for biological applications. Nat Biotechnol 23(12):1517–1526

    Article  CAS  PubMed  Google Scholar 

  • Li W, Szoka FC Jr (2007) Lipid-based nanoparticles for nucleic acid delivery. Pharm Res 24(3):438–449

    Article  PubMed  Google Scholar 

  • Ma L, Reinhardt F, Pan E et al (2010) Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Nat Biotechnol 28(4):341–347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maniataki E, Mourelatos Z (2005) A human, ATP-independent, RISC assembly machine fueled by pre-miRNA. Genes Dev 19(24):2979–2990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marques JT, Devosse T, Wang D et al (2006) A structural basis for discriminating between self and nonself double-stranded RNAs in mammalian cells. Nat Biotechnol 24(5):559–565

    Article  CAS  PubMed  Google Scholar 

  • Martin ME, Rice KG (2007) Peptide-guided gene delivery. AAPS J 9(1):E18–E29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Medina PP, Nolde M, Slack FJ (2010) OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma. Nature 467(7311):86–90

    Article  CAS  PubMed  Google Scholar 

  • Morrissey DV, Lockridge JA, Shaw L et al (2005) Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nat Biotechnol 23(8):1002–1007

    Article  CAS  PubMed  Google Scholar 

  • Nishimura M, Jung EJ, Shah MY et al (2013) Therapeutic synergy between microRNA and siRNA in ovarian cancer treatment. Cancer Discov 3(11):1302–1315

    Article  CAS  PubMed  Google Scholar 

  • Park SM, Gaur AB, Lengyel E et al (2008) The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev 22(7):894–907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Robbins M, Judge A, MacLachlan I (2009) siRNA and innate immunity. Oligonucleotides 19(2):89–102

    Article  CAS  PubMed  Google Scholar 

  • Schickel R, Park SM, Murmann AE et al (2010) miR-200c regulates induction of apoptosis through CD95 by targeting FAP-1. Mol Cell 38(6):908–915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schwarz DS, Hutvagner G, Du T et al (2003) Asymmetry in the assembly of the RNAi enzyme complex. Cell 115(2):199–208

    Article  CAS  PubMed  Google Scholar 

  • Shan G, Li Y, Zhang J et al (2008) A small molecule enhances RNA interference and promotes microRNA processing. Nat Biotechnol 26(8):933–940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sledz CA, Holko M, de Veer MJ et al (2003) Activation of the interferon system by short-interfering RNAs. Nat Cell Biol 5(9):834–839

    Article  CAS  PubMed  Google Scholar 

  • Sokolova V, Epple M (2008) Inorganic nanoparticles as carriers of nucleic acids into cells. Angew Chem Int Ed Engl 47(8):1382–1395

    Article  CAS  PubMed  Google Scholar 

  • Soutschek J, Akinc A, Bramlage B et al (2004) Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432(7014):173–178

    Article  CAS  PubMed  Google Scholar 

  • Takamizawa J, Konishi H, Yanagisawa K et al (2004) Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 64(11):3753–3756

    Article  CAS  PubMed  Google Scholar 

  • Trang P, Medina PP, Wiggins JF et al (2010) Regression of murine lung tumors by the let-7 microRNA. Oncogene 29(11):1580–1587

    Article  CAS  PubMed  Google Scholar 

  • Yang N, Kaur S, Volinia S et al (2008) MicroRNA microarray identifies Let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer. Cancer Res 68(24):10307–10314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zamecnik PC, Stephenson ML (1978) Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide. Proc Natl Acad Sci U S A 75(1):280–284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported, in whole or in part, by the Recruitment Project of Hundred Person of Sun Yat-Sen University (XZ), National Natural Science Foundation 81302262 (XZ), Guangdong Province Science and Technology Project 2015A020212019 (XZ), the Basser Research Center for BRCA (LZ), the National Institutes of Health R01CA142776 (LZ), R01CA190415 (LZ), P50CA083638 (LZ), P50CA174523 (LZ), the Breast Cancer Alliance (LZ), and the Marsha Rivkin Center for Ovarian Cancer Research (LZ).

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Xiaomin Zhong, Dongmei Zhang & Lin Zhang

  2. Center for Stem Cell Biology and Tissue Engineering, Department of Biology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, P.R. China

    Xiaomin Zhong & Minmin Xiong

  3. State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, P.R. China

    Dongmei Zhang

Authors
  1. Xiaomin Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dongmei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Minmin Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiaomin Zhong .

Editor information

Editors and Affiliations

  1. Department of Translational Oncology, Experimental and Clinical Research Center, Charité University Medicine Berlin and Max-Delbrück-Center for Molecular Medicine, Berlin, Berlin, Germany

    Wolfgang Walther

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Zhong, X., Zhang, D., Xiong, M., Zhang, L. (2016). Noncoding RNA for Cancer Gene Therapy. In: Walther, W. (eds) Current Strategies in Cancer Gene Therapy. Recent Results in Cancer Research, vol 209. Springer, Cham. https://doi.org/10.1007/978-3-319-42934-2_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-42934-2_4

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-42932-8

  • Online ISBN: 978-3-319-42934-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation