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Modulating MicroRNA Expression for the Therapy of Pancreatic Cancer

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MicroRNA Targeted Cancer Therapy

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Abstract

Pancreatic cancer is the fourth leading cause of death by cancer worldwide. There is currently no curative treatment excepting surgery for 15 % of patients. Consequently, it is necessary to identify new therapeutic targets such as microRNAs to help manage this disease. Interestingly, these short non-coding RNAs can negatively control the expression of hundreds of genes, and thus are key regulators of tumor progression and dissemination. In addition, they are implicated in cancer cell resistance to treatment. Taken together, microRNAs can represent a new class of molecular targets. MicroRNAs can be combined with different carriers (either non viral or viral) to increase their stability and specificity. Successful examples of microRNA targeting in vivo for the therapy of experimental models of pancreatic cancer have recently emerged. Nevertheless, clinical trials based on microRNA targeting for cancer are still lacking while their interest as biomarkers is emerging. Importantly, improved delivery and specificity to reduce off-target effects must be controlled to accelerate the use of microRNA as new therapeutic targets in oncology.

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References

  1. Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63(1):11–30

    Article  PubMed  Google Scholar 

  2. Iorio MV, Croce CM (2012) MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med 4(3):143–159

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  3. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297

    Article  PubMed  CAS  Google Scholar 

  4. Kim VN, Han J, Siomi MC (2009) Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol 10(2):126–139

    Article  PubMed  CAS  Google Scholar 

  5. Redis RS, Berindan-Neagoe I, Pop VI, Calin GA (2012) Non-coding RNAs as theranostics in human cancers. J Cell Biochem 113(5):1451–1459

    PubMed Central  PubMed  CAS  Google Scholar 

  6. Zhao JL, Rao DS, Boldin MP, Taganov KD, O’Connell RM, Baltimore D (2011) NF-kappaB dysregulation in microRNA-146a-deficient mice drives the development of myeloid malignancies. Proc Natl Acad Sci U S A 108(22):9184–9189

    Article  PubMed Central  PubMed  Google Scholar 

  7. Pan X, Wang Z-X, Wang R (2010) MicroRNA-21: a novel therapeutic target in human cancer. Cancer Biol Ther 10(12):1224–1232

    Article  PubMed  CAS  Google Scholar 

  8. Du Rieu MC, Torrisani J, Selves J, Al Saati T, Souque A, Dufresne M et al (2010) MicroRNA-21 is induced early in pancreatic ductal adenocarcinoma precursor lesions. Clin Chem 56(4):603–612

    Article  PubMed  CAS  Google Scholar 

  9. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E et al (2002) Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 99(24):15524–15529

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  10. Soriano A, Jubierre L, Almazán-Moga A, Molist C, Roma J, de Toledo JS (2013) MicroRNAs as pharmacological targets in cancer. Pharmacol Res Off J Ital Pharmacol Soc 75:3–14

    CAS  Google Scholar 

  11. Nana-Sinkam SP, Croce CM (2011) MicroRNAs as therapeutic targets in cancer. Transl Res J Lab Clin Med 157(4):216–225

    Article  CAS  Google Scholar 

  12. Hanoun N, Delpu Y, Suriawinata AA, Bournet B, Bureau C, Selves J et al (2010) The silencing of microRNA 148a production by DNA hypermethylation is an early event in pancreatic carcinogenesis. Clin Chem 56(7):1107–1118

    Article  PubMed  CAS  Google Scholar 

  13. Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T (2007) Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet 39(5):673–677

    Article  PubMed  CAS  Google Scholar 

  14. Merritt WM, Lin YG, Han LY, Kamat AA, Spannuth WA, Schmandt R et al (2008) Dicer, Drosha, and outcomes in patients with ovarian cancer. N Engl J Med 359(25):2641–2650

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  15. Bloomston M, Frankel WL, Petrocca F, Volinia S, Alder H, Hagan JP et al (2007) MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA J Am Med Assoc 297(17):1901–1908

    Article  CAS  Google Scholar 

  16. Gayral M, Torrisani J, Cordelier P (2014) Current understanding of microRNA as therapeutic targets in cancer. In: Sahu SC (ed) MicroRNAs in toxicology and medicine, 1st edn. Wiley, Chichester, pp 167–172

    Google Scholar 

  17. Jansson MD, Lund AH (2012) MicroRNA and cancer. Mol Oncol 6(6):590–610

    Article  PubMed  CAS  Google Scholar 

  18. Gong C, Yao Y, Wang Y, Liu B, Wu W, Chen J et al (2011) Up-regulation of miR-21 mediates resistance to trastuzumab therapy for breast cancer. J Biol Chem 286(21):19127–19137

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  19. Sicard F, Gayral M, Lulka H, Buscail L, Cordelier P (2013) Targeting miR-21 for the therapy of pancreatic cancer. Mol Ther [Internet]. 2013 Mar 12 [cited 2013 Mar 18]; Available from: http://www.nature.com/doifinder/10.1038/mt.2013.35

  20. Yan H-J, Liu W-S, Sun W-H, Wu J, Ji M, Wang Q (2012) miR-17-5p inhibitor enhances chemosensitivity to gemcitabine via upregulating Bim expression in pancreatic cancer cells. Dig Dis Sci 57(12):3160–3167

    Article  PubMed  CAS  Google Scholar 

  21. Takiuchi D, Eguchi H, Nagano H, Iwagami Y, Tomimaru Y, Wada H et al (2013) Involvement of microRNA-181b in the gemcitabine resistance of pancreatic cancer cells. Pancreatology 13(5):517–523

    Article  PubMed  CAS  Google Scholar 

  22. Di Francesco A, De Pittà C, Moret F, Barbieri V, Celotti L, Mognato M (2013) The DNA-damage response to γ-radiation is affected by miR-27a in A549 cells. Int J Mol Sci 14(9):17881–17896

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  23. Haraguchi T, Ozaki Y, Iba H (2009) Vectors expressing efficient RNA decoys achieve the long-term suppression of specific microRNA activity in mammalian cells. Nucleic Acids Res 37(6):e43

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  24. Pereira DM, Rodrigues PM, Borralho PM, Rodrigues CMP (2013) Delivering the promise of miRNA cancer therapeutics. Drug Discov Today 18(5–6):282–289

    Article  PubMed  CAS  Google Scholar 

  25. Davis S, Lollo B, Freier S, Esau C (2006) Improved targeting of miRNA with antisense oligonucleotides. Nucleic Acids Res 34(8):2294–2304

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  26. Lv H, Zhang S, Wang B, Cui S, Yan J (2006) Toxicity of cationic lipids and cationic polymers in gene delivery. J Control Release 114(1):100–109

    Article  PubMed  CAS  Google Scholar 

  27. Pramanik D, Campbell NR, Karikari C, Chivukula R, Kent OA, Mendell JT et al (2011) Restitution of tumor suppressor microRNAs using a systemic nanovector inhibits pancreatic cancer growth in mice. Mol Cancer Ther 10(8):1470–1480

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  28. Zhang Y, Arrington L, Boardman D, Davis J, Xu Y, Difelice K et al (2013) The development of an in vitro assay to screen lipid based nanoparticles for siRNA delivery. J Control Release 174C:7–14

    Google Scholar 

  29. Chiou G-Y, Cherng J-Y, Hsu H-S, Wang M-L, Tsai C-M, Lu K-H et al (2012) Cationic polyurethanes-short branch PEI-mediated delivery of Mir145 inhibited epithelial-mesenchymal transdifferentiation and cancer stem-like properties and in lung adenocarcinoma. J Control Release 159(2):240–250

    Article  PubMed  CAS  Google Scholar 

  30. Hwang DW, Son S, Jang J, Youn H, Lee S, Lee D et al (2011) A brain-targeted rabies virus glycoprotein-disulfide linked PEI nanocarrier for delivery of neurogenic microRNA. Biomaterials 32(21):4968–4975

    Article  CAS  Google Scholar 

  31. Matsuyama H, Suzuki HI, Nishimori H, Noguchi M, Yao T, Komatsu N (2011) miR-135b mediates NPM-ALK-driven oncogenicity and renders IL-17-producing immunophenotype to anaplastic large cell lymphoma. Blood 118(26):6881–6892

    Article  PubMed  CAS  Google Scholar 

  32. Redis RS, Calin S, Yang Y, You MJ, Calin GA (2012) Cell-to-cell miRNA transfer: from body homeostasis to therapy. Pharmacol Ther 136(2):169–174

    Article  PubMed  CAS  Google Scholar 

  33. Ohno S-I, Takanashi M, Sudo K, Ueda S, Ishikawa A, Matsuyama N et al (2013) Systemically injected exosomes targeted to EGFR deliver antitumor MicroRNA to breast cancer cells. Mol Ther 21(1):185–191

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  34. Kumar MS, Erkeland SJ, Pester RE, Chen CY, Ebert MS, Sharp PA 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  PubMed Central  PubMed  Google Scholar 

  35. Kim S-J, Oh J-S, Shin J-Y, Lee K-D, Sung KW, Nam SJ et al (2011) Development of microRNA-145 for therapeutic application in breast cancer. J Control Release 155(3):427–434

    Article  PubMed  CAS  Google Scholar 

  36. Kota J, Chivukula RR, O’Donnell KA, Wentzel EA, Montgomery CL, Hwang H-W et al (2009) Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 137(6):1005–1017

    Article  PubMed Central  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  38. Hu QL, Jiang QY, Jin X, Shen J, Wang K, Li YB et al (2013) Cationic microRNA-delivering nanovectors with bifunctional peptides for efficient treatment of PANC-1 xenograft model. Biomaterials 34(9):2265–2276

    Article  PubMed  CAS  Google Scholar 

  39. Delpu Y, Lulka H, Sicard F, Saint-Laurent N, Lopez F, Hanoun N et al (2013) The rescue of miR-148a expression in pancreatic cancer: an inappropriate therapeutic tool. Schneider G, editor. PLoS One 8(1):e55513

    Google Scholar 

  40. Torrisani J, Bournet B, du Rieu MC, Bouisson M, Souque A, Escourrou J (2009) let-7 MicroRNA transfer in pancreatic cancer-derived cells inhibits in vitro cell proliferation but fails to alter tumor progression. Hum Gene Ther 20(8):831–844

    Article  PubMed  CAS  Google Scholar 

  41. Janssen HLA, Reesink HW, Lawitz EJ, Zeuzem S, Rodriguez-Torres M, Patel K et al (2013) Treatment of HCV infection by targeting microRNA. N Engl J Med 368(18):1685–1694

    Article  PubMed  CAS  Google Scholar 

  42. O’Neill LA, Sheedy FJ, McCoy CE (2011) MicroRNAs: the fine-tuners of Toll-like receptor signalling. Nat Rev Immunol 11(3):163–175

    Article  PubMed  CAS  Google Scholar 

  43. Jackson AL, Bartz SR, Schelter J, Kobayashi SV, Burchard J, Mao M et al (2003) Expression profiling reveals off-target gene regulation by RNAi. Nat Biotechnol 21(6):635–637

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. INSERM UMR 1037, Bat L3, 1 avenue Jean Poulhès, 84225, 31432, Toulouse Cedex 4, France

    Marion Gayral, Yannick Delpu, Jérôme Torrisani & Pierre Cordelier

  2. Paul Sabatier University Toulouse, Toulouse, France

    Marion Gayral, Yannick Delpu, Jérôme Torrisani & Pierre Cordelier

Authors
  1. Marion Gayral
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  2. Yannick Delpu
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  3. Jérôme Torrisani
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  4. Pierre Cordelier
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Corresponding author

Correspondence to Pierre Cordelier .

Editor information

Editors and Affiliations

  1. Pathology, Wayne State University School of Medicine, Detroit, Michigan, USA

    Fazlul H. Sarkar

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© 2014 Springer International Publishing Switzerland

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Gayral, M., Delpu, Y., Torrisani, J., Cordelier, P. (2014). Modulating MicroRNA Expression for the Therapy of Pancreatic Cancer. In: Sarkar, F. (eds) MicroRNA Targeted Cancer Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-05134-5_11

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