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Effects of miR-155 Antisense Oligonucleotide on Breast Carcinoma Cell Line MDA-MB-157 and Implanted Tumors

  • Zheng, Shu-Rong (Department of Oncology, The First Affiliated Hospital of Wenzhou Medical College) ;
  • Guo, Gui-Long (Department of Oncology, The First Affiliated Hospital of Wenzhou Medical College) ;
  • Zhai, Qi (Department of Oncology, The First Affiliated Hospital of Wenzhou Medical College) ;
  • Zou, Zhang-Yong (Department of Oncology, The First Affiliated Hospital of Wenzhou Medical College) ;
  • Zhang, Wei (Department of Oncology, The First Affiliated Hospital of Wenzhou Medical College)
  • Published : 2013.04.30

Abstract

Diverse studies have shown that miR-155 is overexpressed in different tumor types. However, the precise molecular mechanism of the ectopic expression of miR-155 in breast cancer is still poorly understood. To further explore the role of miR-155 in breast tumorigenesis, we here assessed the influence of miR-155 antisense oligonucleotide (miR-155 ASO) on MDA-MB-157 cell viability and apoptosis in vitro. Furthermore, the effects of inhibitory effects of miR-155 on the growth of xenograft tumors in vivo were determined with performance of immunohistochemistry to detect expression of caspase-3, a pivotal apoptosis regulatory factor, in xenografts. Transfection efficiency detected by laser confocal microscope was higher than 80%. The level of miR-155 expression was significantly decreased (P<0.05) in the cells transfected with miR-155 ASO, compared with that in cells transfected with a negative control. After being transfected with miR-155 ASO, the viability of MDA-MB-157 cells was reduced greatly (P<0.05) and the number of apoptotic cells was increased significantly. Additionally, miR-155 ASO inhibited the growth of transplanted tumor in vivo and significantly increased the expression of caspase-3. Taken together, our study revealed that miR-155 ASO can induce cell apoptosis and inhibit cell proliferation in vitro. Moreover, miR-155 ASO could significantly repress tumor growth in vivo, presumably by inducing apoptosis via caspase-3 up-regulation. These findings provide experimental evidence for using miR-155 as a therapeutic target of breast carcinoma.

References

  1. Zheng SR, Guo GL, Zhang W, et al (2012). Clinical significance of miR-155 expression in breast cancer and effects of miR-155 ASO on cell viability and apoptosis. Oncol Rep, 27, 1149-55.
  2. Bhattacharyya S, Balakathiresan NS, Dalgard C, et al (2011). Elevated miR-155 promotes inflammation in cystic fibrosis by driving hyperexpression of interleukin-8. J Biol Chem, 286, 11604-15. https://doi.org/10.1074/jbc.M110.198390
  3. Brennecke J, Hipfner DR, Stark A, Russell RB, Cohen SM (2003). Bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell, 113, 25-36. https://doi.org/10.1016/S0092-8674(03)00231-9
  4. Busch M, Zernecke A (2012). microRNAs in the regulation of dendritic cell functions in inflammation and atherosclerosis. J Mol Med (Berl), 90, 877-85. https://doi.org/10.1007/s00109-012-0864-5
  5. Chen CZ, Li L, Lodish HF, Bartel DP (2004). MicroRNAs modulate hematopoietic lineage differentiation. Science, 303, 83-6. https://doi.org/10.1126/science.1091903
  6. Ambros V (2003). MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell, 113, 673-6. https://doi.org/10.1016/S0092-8674(03)00428-8
  7. Bartel DP (2009). MicroRNAs: target recognition and regulatory functions. Cell, 136, 215-33. https://doi.org/10.1016/j.cell.2009.01.002
  8. Dong F, Lou D (2012). MicroRNA-34b/c suppresses uveal melanoma cell proliferation and migration through multiple targets. Mol Vis, 18, 537-46.
  9. Donnem T, Fenton CG, Lonvik K, et al (2012). MicroRNA signatures in tumor tissue related to angiogenesis in nonsmall cell lung cancer. PLoS One, 7, e29671. https://doi.org/10.1371/journal.pone.0029671
  10. Ghorpade DS, Leyland R, Kurowska-Stolarska M, Patil SA, Balaji KN (2012). MicroRNA-155 Is Required for Mycobacterium bovis BCG-Mediated Apoptosis of Macrophages. Mol Cell Biol, 32, 2239-53. https://doi.org/10.1128/MCB.06597-11
  11. Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ (2006). miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res, 34 (Database issue), D140-4. https://doi.org/10.1093/nar/gkj112
  12. Hammond SM (2007). MicroRNAs as tumor suppressors. Nat Genet, 39, 582-3.
  13. Hayashita Y, Osada H, Tatematsu Y, et al (2005). A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res, 65, 9628-32. https://doi.org/10.1158/0008-5472.CAN-05-2352
  14. He L, Thomson JM, Hemann MT, et al (2005). A microRNA polycistron as a potential human oncogene. Nature, 435, 828-33. https://doi.org/10.1038/nature03552
  15. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  16. Jiang S, Zhang HW, Lu MH, et al (2010). MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene. Cancer Res, 70, 3119-27. https://doi.org/10.1158/0008-5472.CAN-09-4250
  17. Kong W, He L, Coppola M, et al (2010). MicroRNA-155 regulates cell survival, growth, and chemosensitivity by targeting FOXO3a in breast cancer. J Biol Chem, 285, 17869-79. https://doi.org/10.1074/jbc.M110.101055
  18. Lee RC, Feinbaum RL, Ambros V (1993). elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell, 75, 843-54. https://doi.org/10.1016/0092-8674(93)90529-Y
  19. Li J, Huang H, Sun L, et al (2009). MiR-21 Indicates Poor Prognosis in Tongue Squamous Cell Carcinomas as an Apoptosis Inhibitor. Clin Cancer Res, 15, 3998-4008. https://doi.org/10.1158/1078-0432.CCR-08-3053
  20. Li Y, Zhu X, Gu J, et al (2010). Anti-miR-21 oligonucleotide enhances chemosensitivity of leukemic HL60 cells to arabinosylcytosine by inducing apoptosis. Hematology, 15, 215-21. https://doi.org/10.1179/102453310X12647083620840
  21. Louafi F, Martinez-Nunez RT, Sanchez-Elsner T (2010). MicroRNA-155 targets SMAD2 and modulates the response of macrophages to transforming growth factor-{beta}. J Biol Chem, 285, 41328-36. https://doi.org/10.1074/jbc.M110.146852
  22. O'Connell RM, Kahn D, Gibson WS, et al (2010). MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development. Immunity, 33, 607-19. https://doi.org/10.1016/j.immuni.2010.09.009
  23. Oertli M, Engler DB, Kohler E, et al (2011). MicroRNA-155 is essential for the T cell-mediated control of Helicobacter pylori infection and for the induction of chronic Gastritis and Colitis. J Immuno, 187, 3578-86. https://doi.org/10.4049/jimmunol.1101772
  24. Ovcharenko D, Kelnar K, Johnson C, Leng N, Brown D (2007). Genome-scale microRNA and small interfering RNA screens identify small RNA modulators of TRAIL-induced apoptosis pathway. Cancer Res, 67, 10782-8. https://doi.org/10.1158/0008-5472.CAN-07-1484
  25. Papagiannakopoulos T, Shapiro A, Kosik KS (2008). MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. Cancer Res, 68, 8164-72. https://doi.org/10.1158/0008-5472.CAN-08-1305
  26. Porter AG, J nicke RU (1999). Emerging roles of caspase-3 in apoptosis. Cell Death Differ, 6, 99-100. https://doi.org/10.1038/sj.cdd.4400476
  27. Tam W, Dahlberg JE (2006). miR-155/BIC as an oncogenic microRNA. Genes Chromosomes Cancer, 45, 211-2. https://doi.org/10.1002/gcc.20282
  28. Urbich C, Kuehbacher A, Dimmeler S (2008). Role of microRNAs in vascular diseases, inflammation, and angiogenesis. Cardiovasc Res, 79, 581-8. https://doi.org/10.1093/cvr/cvn156
  29. Vasilatou D, Papageorgiou S, Pappa V, Papageorgiou E, Dervenoulas J (2010). The role of microRNAs in normal and malignant hematopoiesis. Eur J Haematol, 84, 1-16. https://doi.org/10.1111/j.1600-0609.2009.01348.x
  30. Wang HQ, Yu XD, Liu ZH, et al (2011). Deregulated miR-155 promotes Fas-mediated apoptosis in human intervertebral disc degeneration by targeting FADD and caspase-3. J Pathol, 225, 232-42. https://doi.org/10.1002/path.2931
  31. Yao R, Ma Y, Du Y, et al (2011). The altered expression of inflammation-related microRNAs with microRNA-155 expression correlates with Th17 differentiation in patients with acute coronary syndrome. Cell Mol Immunol, 8, 486-95. https://doi.org/10.1038/cmi.2011.22
  32. Yin Q, Wang X, Fewell C, et al (2010). MicroRNA miR-155 inhibits bone morphogenetic protein (BMP) signaling and BMP-mediated Epstein-Barr virus reactivation. J Virol, 84, 6318-27. https://doi.org/10.1128/JVI.00635-10
  33. Yip L, Kelly L, Shuai Y, et al (2011). MicroRNA signature distinguishes the degree of aggressiveness of papillary thyroid carcinoma. Ann Surg Oncol, 18, 2035-41. https://doi.org/10.1245/s10434-011-1733-0
  34. Yu Z, Jian Z, Shen SH, Purisima E, Wang E (2007). Global analysis of microRNA target gene expression reveals that miRNA targets are lower expressed in mature mouse and Drosophila tissues than in the embryos. Nucleic Acids Res, 35, 152-64.
  35. Zhang RG, Zhang RP, Wang XW, Xie H (2002). Effects of cisplatin on telomerase activity and telomere length in BEL-7404 human hepatoma cells. Cell Res, 12, 55-62. https://doi.org/10.1038/sj.cr.7290110

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