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.
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References
Olena AF, Patton JG . Genomic organization of microRNAs. J Cell Physiol 2010; 222: 540–545.
Friedman JM, Jones PA . MicroRNAs: critical mediators of differentiation, development and disease. Swiss Med Wkly 2009; 139: 466–472.
Vasudevan S, Tong Y, Steitz JA . Switching from repression to activation: microRNAs can up-regulate translation. Science 2007; 318: 1931–1934.
Chua JH, Armugam A, Jeyaseelan K . MicroRNAs: biogenesis, function and applications. Curr Opin Mol Ther 2009; 11: 189–199.
Iwasaki S, Tomari Y . Argonaute-mediated translational repression (and activation). Fly (Austin) 2009; 3: 204–206.
Saunders MA, Lim LP . (micro)Genomic medicine: microRNAs as therapeutics and biomarkers. RNA Biol 2009; 6: 324–328.
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.
Tang JT, Fang JY . MicroRNA regulatory network in human colorectal cancer. Mini Rev Med Chem 2009; 9: 921–926.
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.
Valeri N, Croce CM, Fabbri M . Pathogenetic and clinical relevance of microRNAs in colorectal cancer. Cancer Genomics Proteomics 2009; 6: 195–204.
Faber C, Kirchner T, Hlubek F . The impact of microRNAs on colorectal cancer. Virchows Arch 2009; 454: 359–367.
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.
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.
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.
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.
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.
Planelles L, Medema JP, Hahne M, Hardenberg G . The expanding role of APRIL in cancer and immunity. Curr Mol Med 2008; 8: 829–844.
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.
Moreaux J, Veyrune JL, De Vos J, Klein B . APRIL is overexpressed in cancer: link with tumor progression. BMC Cancer 2009; 9: 83.
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.
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.
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.
Center MM, Jemal A, Smith RA, Ward E . Worldwide variations in colorectal cancer. CA Cancer J Clin 2009; 59: 366–378.
Markowitz SD, Bertagnolli MM . Molecular origins of cancer: molecular basis of colorectal cancer. N Engl J Med 2009; 361: 2449–2460.
Ortega J, Vigil CE, Chodkiewicz C . Current progress in targeted therapy for colorectal cancer. Cancer Control 2010; 17: 7–15.
Dykxhoorn DM . RNA interference as an anticancer therapy: a patent perspective. Expert Opin Ther Pat 2009; 19: 475–491.
Wang SL, Yao HH, Qin ZH . Strategies for short hairpin RNA delivery in cancer gene therapy. Expert Opin Biol Ther 2009; 9: 1357–1368.
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.
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.
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.
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.
Satyanarayana A, Kaldis P . Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms. Oncogene 2009; 28: 2925–2939.
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.
Malumbres M, Barbacid M . Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 2009; 9: 153–166.
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.
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.
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.
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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
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DOI: https://doi.org/10.1038/cgt.2011.19
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