Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Identification of microRNA-target interaction in APRIL-knockdown colorectal cancer cells

Abstract

MicroRNAs (miRNAs) regulate mammalian gene expression by targeting mRNAs and have key roles in several cellular processes, including differentiation, development, apoptosis and cancer pathomechanisms. Our previous studies have confirmed that a proliferation-inducing ligand (APRIL) gene is overexpressed in colorectal cancer (CRC) tumors and SW480 cells. To study the potential mechanisms of APRIL gene in the occurrence and development of the CRC, herein, we investigated whether APRIL-knockdown had the inhibitory effect on the growth of SW480 cells and had the simultaneous expression changes of miRNAs and mRNAs by microarrays. Our results suggest that siRNA-APRIL can effectively inhibit the growth of SW480 cells in vitro and in vivo and several miRNAs via specific pathways might be involved in regulating the phenotype of loss-of-function in APRIL-knockdown SW480 cells. Thus, our study highlights the possible mechanisms of miRNA-target regulating the function of APRIL gene in CRC cells, moreover, siRNA-APRIL holds great promise as a novel gene therapy approach for APRIL- positive CRC treatment.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Olena AF, Patton JG . Genomic organization of microRNAs. J Cell Physiol 2010; 222: 540–545.

    CAS  PubMed Central  PubMed  Google Scholar 

  2. Friedman JM, Jones PA . MicroRNAs: critical mediators of differentiation, development and disease. Swiss Med Wkly 2009; 139: 466–472.

    CAS  PubMed Central  PubMed  Google Scholar 

  3. Vasudevan S, Tong Y, Steitz JA . Switching from repression to activation: microRNAs can up-regulate translation. Science 2007; 318: 1931–1934.

    Article  CAS  PubMed  Google Scholar 

  4. Chua JH, Armugam A, Jeyaseelan K . MicroRNAs: biogenesis, function and applications. Curr Opin Mol Ther 2009; 11: 189–199.

    CAS  PubMed  Google Scholar 

  5. Iwasaki S, Tomari Y . Argonaute-mediated translational repression (and activation). Fly (Austin) 2009; 3: 204–206.

    Article  Google Scholar 

  6. Saunders MA, Lim LP . (micro)Genomic medicine: microRNAs as therapeutics and biomarkers. RNA Biol 2009; 6: 324–328.

    Article  CAS  PubMed  Google Scholar 

  7. Yang BF, Lu YJ, Wang ZG . MicroRNAs and apoptosis: implications in the molecular therapy of human disease. Clin Exp Pharmacol Physiol 2009; 36: 951–960.

    Article  CAS  PubMed  Google Scholar 

  8. Tang JT, Fang JY . MicroRNA regulatory network in human colorectal cancer. Mini Rev Med Chem 2009; 9: 921–926.

    Article  CAS  PubMed  Google Scholar 

  9. Motoyama K, Inoue H, Takatsuno Y, Tanaka F, Mimori K, Uetake H et al. Over- and under-expressed microRNAs in human colorectal cancer. Int J Oncol 2009; 34: 1069–1075.

    CAS  PubMed  Google Scholar 

  10. Valeri N, Croce CM, Fabbri M . Pathogenetic and clinical relevance of microRNAs in colorectal cancer. Cancer Genomics Proteomics 2009; 6: 195–204.

    CAS  PubMed  Google Scholar 

  11. Faber C, Kirchner T, Hlubek F . The impact of microRNAs on colorectal cancer. Virchows Arch 2009; 454: 359–367.

    Article  CAS  PubMed  Google Scholar 

  12. Hahne M, Kataoka T, Schroter M, Hofmann K, Irmler M, Bodmer JL et al. APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth. J Exp Med 1998; 188: 1185–1190.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gu D, Ge J, Du W, Xue F, Chen Z, Zhao H et al. Raised expression of APRIL in Chinese patients with immune thrombocytopenia and its clinical implications. Autoimmunity 2009; 42: 692–698.

    Article  CAS  PubMed  Google Scholar 

  14. Kimberley FC, van Bostelen L, Cameron K, Hardenberg G, Marquart JA, Hahne M et al. The proteoglycan (heparan sulfate proteoglycan) binding domain of APRIL serves as a platform for ligand multimerization and cross-linking. FASEB J 2009; 23: 1584–1595.

    Article  CAS  PubMed  Google Scholar 

  15. Sun B, Wang H, Wang X, Huang H, Ding W, Jing R et al. A proliferation- inducing ligand: a new biomarker for non-small cell lung cancer. Exp Lung Res 2009; 35: 486–500.

    Article  CAS  PubMed  Google Scholar 

  16. Mhawech-Fauceglia P, Kaya G, Sauter G, McKee T, Donze O, Schwaller J et al. The source of APRIL up-regulation in human solid tumor lesions. J Leukoc Biol 2006; 80: 697–704.

    Article  CAS  PubMed  Google Scholar 

  17. Planelles L, Medema JP, Hahne M, Hardenberg G . The expanding role of APRIL in cancer and immunity. Curr Mol Med 2008; 8: 829–844.

    Article  CAS  PubMed  Google Scholar 

  18. Wang F, Chen L, Mao ZB, Shao JG, Tan C, Huang WD . Lentivirus- mediated short hairpin RNA targeting the APRIL gene suppresses the growth of pancreatic cancer cells in vitro and in vivo. Oncol Rep 2008; 20: 135–139.

    CAS  PubMed  Google Scholar 

  19. Moreaux J, Veyrune JL, De Vos J, Klein B . APRIL is overexpressed in cancer: link with tumor progression. BMC Cancer 2009; 9: 83.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Ding W, Wang J, Sun B, Ju S, Yuan H, Wang X et al. APRIL knockdown suppresses migration and invasion of human colon carcinoma cells. Clin Biochem 2009; 42: 1694–1698.

    Article  CAS  PubMed  Google Scholar 

  21. Irizarry RA, Bolstad BM, Collin F, Cope LM, Hobbs B, Speed TP . Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res 2003; 31: e15.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U et al. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 2003; 4: 249–264.

    Article  PubMed  Google Scholar 

  23. Center MM, Jemal A, Smith RA, Ward E . Worldwide variations in colorectal cancer. CA Cancer J Clin 2009; 59: 366–378.

    Article  PubMed  Google Scholar 

  24. Markowitz SD, Bertagnolli MM . Molecular origins of cancer: molecular basis of colorectal cancer. N Engl J Med 2009; 361: 2449–2460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ortega J, Vigil CE, Chodkiewicz C . Current progress in targeted therapy for colorectal cancer. Cancer Control 2010; 17: 7–15.

    Article  PubMed  Google Scholar 

  26. Dykxhoorn DM . RNA interference as an anticancer therapy: a patent perspective. Expert Opin Ther Pat 2009; 19: 475–491.

    Article  CAS  PubMed  Google Scholar 

  27. Wang SL, Yao HH, Qin ZH . Strategies for short hairpin RNA delivery in cancer gene therapy. Expert Opin Biol Ther 2009; 9: 1357–1368.

    Article  CAS  PubMed  Google Scholar 

  28. Gregersen LH, Jacobsen AB, Frankel LB, Wen J, Krogh A, Lund AH . MicroRNA-145 targets YES and STAT1 in colon cancer cells. PLoS One 2010; 5: e8836.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Schepeler T, Reinert JT, Ostenfeld MS, Christensen LL, Silahtarogl AN, Dyrskjot L et al. Diagnostic and prognostic microRNAs in stage II colon cancer. Cancer Res 2008; 68: 6416–6424.

    Article  CAS  PubMed  Google Scholar 

  30. Wang CJ, Zhou ZG, Wang L, Yang L, Zhou B, Gu J et al. Clinicopathological significance of microRNA-31, -143 and -145 expression in colorectal cancer. Dis Markers 2009; 26: 27–34.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Slaby O, Svoboda M, Fabian P, Smerdova T, Knoflickova D, Bednarikova M et al. Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Oncology 2007; 72: 397–402.

    Article  CAS  PubMed  Google Scholar 

  32. Satyanarayana A, Kaldis P . Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms. Oncogene 2009; 28: 2925–2939.

    Article  CAS  PubMed  Google Scholar 

  33. Kapuy O, He E, Lopez-Aviles S, Uhlmann F, Tyson JJ, Novak B . System-level feedbacks control cell cycle progression. FEBS Lett 2009; 583: 3992–3998.

    Article  CAS  PubMed  Google Scholar 

  34. Malumbres M, Barbacid M . Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 2009; 9: 153–166.

    Article  CAS  PubMed  Google Scholar 

  35. Li J, Min R, Bonner A, Zhang Z . A probabilistic framework to improve microrna target prediction by incorporating proteomics data. J Bioinform Comput Biol 2009; 7: 955–972.

    Article  CAS  PubMed  Google Scholar 

  36. Selbach M, Schwanhausser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N . Widespread changes in protein synthesis induced by microRNAs. Nature 2008; 455: 58–63.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by grant XK200723 from Key Laboratory Subject of Jiangsu Province and Natural Science Foundation of Nantong University (No. 09Z043.10Z064). We gratefully acknowledge the participation of Guihua Wang, Jie Meng and Haiquan Li.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to H Wang.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on Cancer Gene Therapy website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, F., Ding, W., Wang, J. et al. Identification of microRNA-target interaction in APRIL-knockdown colorectal cancer cells. Cancer Gene Ther 18, 500–509 (2011). https://doi.org/10.1038/cgt.2011.19

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/cgt.2011.19

Keywords

This article is cited by

Search

Quick links