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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78636完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 胡忠怡 | |
| dc.contributor.author | Ke-Wei Wang | en |
| dc.contributor.author | 王克巍 | zh_TW |
| dc.date.accessioned | 2021-07-11T15:08:52Z | - |
| dc.date.available | 2022-08-15 | |
| dc.date.copyright | 2019-08-28 | |
| dc.date.issued | 2019 | |
| dc.date.submitted | 2019-08-12 | |
| dc.identifier.citation | 1. Westermann, F. and M. Schwab, Genetic parameters of neuroblastomas. Cancer Lett, 2002. 184(2): p. 127-47.
2. Gehring, M., F. Berthold, L. Edler, M. Schwab, and L.C. Amler, The 1p deletion is not a reliable marker for the prognosis of patients with neuroblastoma. Cancer Res, 1995. 55(22): p. 5366-9. 3. Maris, J.M., Recent advances in neuroblastoma. N Engl J Med, 2010. 362(23): p. 2202-11. 4. Brodeur, G.M., Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer, 2003. 3(3): p. 203-16. 5. Brodeur, G.M. and A. Nakagawara, Molecular basis of clinical heterogeneity in neuroblastoma. Am J Pediatr Hematol Oncol, 1992. 14(2): p. 111-6. 6. Institute, N.C. PDQ® Unusual Cancers of Childhood Treatment. https://www.cancer.gov/types/neuroblastoma/hp 7. 中華民國兒童癌症基金會 http://www.ccfroc.org.tw/index.php 8. Mosse, Y.P., M. Laudenslager, L. Longo, K.A. Cole, A. Wood, E.F. Attiyeh, M.J. Laquaglia, R. Sennett, J.E. Lynch, P. Perri, G. Laureys, F. Speleman, C. Kim, C. Hou, H. Hakonarson, A. Torkamani, N.J. Schork, G.M. Brodeur, G.P. Tonini, E. Rappaport, M. Devoto, and J.M. Maris, Identification of ALK as a major familial neuroblastoma predisposition gene. Nature, 2008. 455(7215): p. 930-5. 9. Gestblom, C., A. Grynfeld, I. Ora, E. Ortoft, C. Larsson, H. Axelson, B. Sandstedt, P. Cserjesi, E.N. Olson, and S. Pahlman, The basic helix-loop-helix transcription factor dHAND, a marker gene for the developing human sympathetic nervous system, is expressed in both high- and low-stage neuroblastomas. Lab Invest, 1999. 79(1): p. 67-79. 10. Hoehner, J.C., C. Gestblom, L. Olsen, and S. Pahlman, Spatial association of apoptosis-related gene expression and cellular death in clinical neuroblastoma. Br J Cancer, 1997. 75(8): p. 1185-94. 11. Pugh, T.J., O. Morozova, E.F. Attiyeh, S. Asgharzadeh, J.S. Wei, D. Auclair, S.L. Carter, K. Cibulskis, M. Hanna, A. Kiezun, J. Kim, M.S. Lawrence, L. Lichenstein, A. McKenna, C.S. Pedamallu, A.H. Ramos, E. Shefler, A. Sivachenko, C. Sougnez, C. Stewart, A. Ally, I. Birol, R. Chiu, R.D. Corbett, M. Hirst, S.D. Jackman, B. Kamoh, A.H. Khodabakshi, M. Krzywinski, A. Lo, R.A. Moore, K.L. Mungall, J. Qian, A. Tam, N. Thiessen, Y. Zhao, K.A. Cole, M. Diamond, S.J. Diskin, Y.P. Mosse, A.C. Wood, L. Ji, R. Sposto, T. Badgett, W.B. London, Y. Moyer, J.M. Gastier-Foster, M.A. Smith, J.M. Guidry Auvil, D.S. Gerhard, M.D. Hogarty, S.J. Jones, E.S. Lander, S.B. Gabriel, G. Getz, R.C. Seeger, J. Khan, M.A. Marra, M. Meyerson, and J.M. Maris, The genetic landscape of high-risk neuroblastoma. Nat Genet, 2013. 45(3): p. 279-84. 12. Maris, J.M., M.D. Hogarty, R. Bagatell, and S.L. Cohn, Neuroblastoma. Lancet, 2007. 369(9579): p. 2106-20. 13. Agarwal, S., G. Milazzo, K. Rajapakshe, R. Bernardi, Z. Chen, E. Barberi, J. Koster, G. Perini, C. Coarfa, and J.M. Shohet, MYCN acts as a direct co-regulator of p53 in MYCN amplified neuroblastoma. Oncotarget, 2018. 9(29): p. 20323-20338. 14. Dzieran, J., A. Rodriguez Garcia, U.K. Westermark, A.B. Henley, E. Eyre Sanchez, C. Trager, H.J. Johansson, J. Lehtio, and M. Arsenian-Henriksson, MYCN-amplified neuroblastoma maintains an aggressive and undifferentiated phenotype by deregulation of estrogen and NGF signaling. Proc Natl Acad Sci U S A, 2018. 115(6): p. E1229-e1238. 15. Menard, M., C. Costechareyre, G. Ichim, J. Blachier, D. Neves, L. Jarrosson-Wuilleme, R. Depping, J. Koster, P. Saintigny, P. Mehlen, and S. Tauszig-Delamasure, Hey1- and p53-dependent TrkC proapoptotic activity controls neuroblastoma growth. PLoS Biol, 2018. 16(5): p. e2002912. 16. White, P.S., J.M. Maris, C. Beltinger, E. Sulman, H.N. Marshall, M. Fujimori, B.A. Kaufman, J.A. Biegel, C. Allen, C. Hilliard, M.B. Valentine, A.T. Look, H. Enomoto, S. Sakiyama, and G.M. Brodeur, A region of consistent deletion in neuroblastoma maps within human chromosome 1p36.2-36.3. Proc Natl Acad Sci U S A, 1995. 92(12): p. 5520-4. 17. Bresler, S.C., D.A. Weiser, P.J. Huwe, J.H. Park, K. Krytska, H. Ryles, M. Laudenslager, E.F. Rappaport, A.C. Wood, P.W. McGrady, M.D. Hogarty, W.B. London, R. Radhakrishnan, M.A. Lemmon, and Y.P. Mosse, ALK mutations confer differential oncogenic activation and sensitivity to ALK inhibition therapy in neuroblastoma. Cancer Cell, 2014. 26(5): p. 682-94. 18. Janoueix-Lerosey, I., D. Lequin, L. Brugieres, A. Ribeiro, L. de Pontual, V. Combaret, V. Raynal, A. Puisieux, G. Schleiermacher, G. Pierron, D. Valteau-Couanet, T. Frebourg, J. Michon, S. Lyonnet, J. Amiel, and O. Delattre, Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma. Nature, 2008. 455(7215): p. 967-70. 19. Brodeur, G.M., R.C. Seeger, M. Schwab, H.E. Varmus, and J.M. Bishop, Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science, 1984. 224(4653): p. 1121-4. 20. Weiss, W.A., K. Aldape, G. Mohapatra, B.G. Feuerstein, and J.M. Bishop, Targeted expression of MYCN causes neuroblastoma in transgenic mice. Embo j, 1997. 16(11): p. 2985-95. 21. Katzenstein, H.M., P.M. Kent, W.B. London, and S.L. Cohn, Treatment and outcome of 83 children with intraspinal neuroblastoma: the Pediatric Oncology Group experience. J Clin Oncol, 2001. 19(4): p. 1047-55. 22. De Bernardi, B., C. Pianca, P. Pistamiglio, E. Veneselli, E. Viscardi, A. Pession, P. Alvisi, M. Carli, A. Donfrancesco, F. Casale, M.G. Giuliano, L.C. di Montezemolo, A. Di Cataldo, M. Lo Curto, S. Bagnulo, R.F. Schumacher, A. Tamburini, A. Garaventa, L. Clemente, and P. Bruzzi, Neuroblastoma with symptomatic spinal cord compression at diagnosis: treatment and results with 76 cases. J Clin Oncol, 2001. 19(1): p. 183-90. 23. Plantaz, D., H. Rubie, J. Michon, F. Mechinaud, C. Coze, P. Chastagner, D. Frappaz, M. Gigaud, J.G. Passagia, and O. Hartmann, The treatment of neuroblastoma with intraspinal extension with chemotherapy followed by surgical removal of residual disease. A prospective study of 42 patients--results of the NBL 90 Study of the French Society of Pediatric Oncology. Cancer, 1996. 78(2): p. 311-9. 24. Cohen, L.M., A. Elliott, and S.K. Freitag, Acquired Intermittent Pediatric Horner Syndrome due to Neuroblastoma. Ophthalmic Plast Reconstr Surg, 2018. 34(2): p. e38-e41. 25. Quinn, J.J. and A.J. Altman, The multiple hematologic manifestations of neuroblastoma. Am J Pediatr Hematol Oncol, 1979. 1(3): p. 201-5. 26. Kapoor, P.G. and R. Chabbra, Neuroblastoma presenting as raccoon eyes. J Pediatr, 2014. 164(6): p. 1495. 27. Matthay, K.K., Stage 4S neuroblastoma: what makes it special? J Clin Oncol, 1998. 16(6): p. 2003-6. 28. D'Angio, G.J., A.E. Evans, and C.E. Koop, Special pattern of widespread neuroblastoma with a favourable prognosis. Lancet, 1971. 1(7708): p. 1046-9. 29. Geatti, O., B. Shapiro, J.C. Sisson, R.J. Hutchinson, S. Mallette, P. Eyre, and W.H. Beierwaltes, Iodine-131 metaiodobenzylguanidine scintigraphy for the location of neuroblastoma: preliminary experience in ten cases. J Nucl Med, 1985. 26(7): p. 736-42. 30. Rufini, V., G.A. Fisher, B.L. Shulkin, J.C. Sisson, and B. Shapiro, Iodine-123-MIBG imaging of neuroblastoma: utility of SPECT and delayed imaging. J Nucl Med, 1996. 37(9): p. 1464-8. 31. Evans, A.E., G.J. D'Angio, K. Propert, J. Anderson, and H.W. Hann, Prognostic factor in neuroblastoma. Cancer, 1987. 59(11): p. 1853-9. 32. Brodeur, G.M., J. Pritchard, F. Berthold, N.L. Carlsen, V. Castel, R.P. Castelberry, B. De Bernardi, A.E. Evans, M. Favrot, F. Hedborg, and et al., Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol, 1993. 11(8): p. 1466-77. 33. Cangemi, G., G. Reggiardo, S. Barco, L. Barbagallo, M. Conte, P. D'Angelo, M. Bianchi, C. Favre, B. Galleni, G. Melioli, R. Haupt, A. Garaventa, and M.V. Corrias, Prognostic value of ferritin, neuron-specific enolase, lactate dehydrogenase, and urinary and plasmatic catecholamine metabolites in children with neuroblastoma. Onco Targets Ther, 2012. 5: p. 417-23. 34. Shimada, H., I.M. Ambros, L.P. Dehner, J. Hata, V.V. Joshi, B. Roald, D.O. Stram, R.B. Gerbing, J.N. Lukens, K.K. Matthay, and R.P. Castleberry, The International Neuroblastoma Pathology Classification (the Shimada system). Cancer, 1999. 86(2): p. 364-72. 35. Lonergan, G.J., C.M. Schwab, E.S. Suarez, and C.L. Carlson, Neuroblastoma, ganglioneuroblastoma, and ganglioneuroma: radiologic-pathologic correlation. Radiographics, 2002. 22(4): p. 911-34. 36. Shimada, H., S. Umehara, Y. Monobe, Y. Hachitanda, A. Nakagawa, S. Goto, R.B. Gerbing, D.O. Stram, J.N. Lukens, and K.K. Matthay, International neuroblastoma pathology classification for prognostic evaluation of patients with peripheral neuroblastic tumors: a report from the Children's Cancer Group. Cancer, 2001. 92(9): p. 2451-61. 37. Giannini, G., F. Cerignoli, M. Mellone, I. Massimi, C. Ambrosi, C. Rinaldi, C. Dominici, L. Frati, I. Screpanti, and A. Gulino, High mobility group A1 is a molecular target for MYCN in human neuroblastoma. Cancer Res, 2005. 65(18): p. 8308-16. 38. Chen, L., N. Iraci, S. Gherardi, L.D. Gamble, K.M. Wood, G. Perini, J. Lunec, and D.A. Tweddle, p53 is a direct transcriptional target of MYCN in neuroblastoma. Cancer Res, 2010. 70(4): p. 1377-88. 39. Hatzi, E., C. Murphy, A. Zoephel, H. Ahorn, U. Tontsch, A.M. Bamberger, K. Yamauchi-Takihara, L. Schweigerer, and T. Fotsis, N-myc oncogene overexpression down-regulates leukemia inhibitory factor in neuroblastoma. Eur J Biochem, 2002. 269(15): p. 3732-41. 40. Sawai, S., A. Shimono, Y. Wakamatsu, C. Palmes, K. Hanaoka, and H. Kondoh, Defects of embryonic organogenesis resulting from targeted disruption of the N-myc gene in the mouse. Development, 1993. 117(4): p. 1445-55. 41. Spitz, R., B. Hero, K. Ernestus, and F. Berthold, Deletions in chromosome arms 3p and 11q are new prognostic markers in localized and 4s neuroblastoma. Clin Cancer Res, 2003. 9(1): p. 52-8. 42. Attiyeh, E.F., W.B. London, Y.P. Mosse, Q. Wang, C. Winter, D. Khazi, P.W. McGrady, R.C. Seeger, A.T. Look, H. Shimada, G.M. Brodeur, S.L. Cohn, K.K. Matthay, and J.M. Maris, Chromosome 1p and 11q deletions and outcome in neuroblastoma. N Engl J Med, 2005. 353(21): p. 2243-53. 43. Plantaz, D., J. Vandesompele, N. Van Roy, M. Lastowska, N. Bown, V. Combaret, M.C. Favrot, O. Delattre, J. Michon, J. Benard, O. Hartmann, J.C. Nicholson, F.M. Ross, C. Brinkschmidt, G. Laureys, H. Caron, K.K. Matthay, B.G. Feuerstein, and F. Speleman, Comparative genomic hybridization (CGH) analysis of stage 4 neuroblastoma reveals high frequency of 11q deletion in tumors lacking MYCN amplification. Int J Cancer, 2001. 91(5): p. 680-6. 44. Bown, N., S. Cotterill, M. Lastowska, S. O'Neill, A.D. Pearson, D. Plantaz, M. Meddeb, G. Danglot, C. Brinkschmidt, H. Christiansen, G. Laureys, F. Speleman, J. Nicholson, A. Bernheim, D.R. Betts, J. Vandesompele, and N. Van Roy, Gain of chromosome arm 17q and adverse outcome in patients with neuroblastoma. N Engl J Med, 1999. 340(25): p. 1954-61. 45. Janoueix-Lerosey, I., G. Schleiermacher, E. Michels, V. Mosseri, A. Ribeiro, D. Lequin, J. Vermeulen, J. Couturier, M. Peuchmaur, A. Valent, D. Plantaz, H. Rubie, D. Valteau-Couanet, C. Thomas, V. Combaret, R. Rousseau, A. Eggert, J. Michon, F. Speleman, and O. Delattre, Overall genomic pattern is a predictor of outcome in neuroblastoma. J Clin Oncol, 2009. 27(7): p. 1026-33. 46. Look, A.T., F.A. Hayes, R. Nitschke, N.B. McWilliams, and A.A. Green, Cellular DNA content as a predictor of response to chemotherapy in infants with unresectable neuroblastoma. N Engl J Med, 1984. 311(4): p. 231-5. 47. Joshi, V.V., A.B. Cantor, G.M. Brodeur, A.T. Look, J.J. Shuster, G. Altshuler, E.W. Larkin, C.T. Holbrook, J.F. Silverman, H.T. Norris, and et al., Correlation between morphologic and other prognostic markers of neuroblastoma. A study of histologic grade, DNA index, N-myc gene copy number, and lactic dehydrogenase in patients in the Pediatric Oncology Group. Cancer, 1993. 71(10): p. 3173-81. 48. Nakagawara, A., C.G. Azar, N.J. Scavarda, and G.M. Brodeur, Expression and function of TRK-B and BDNF in human neuroblastomas. Mol Cell Biol, 1994. 14(1): p. 759-67. 49. Ryden, M., R. Sehgal, C. Dominici, F.H. Schilling, C.F. Ibanez, and P. Kogner, Expression of mRNA for the neurotrophin receptor trkC in neuroblastomas with favourable tumour stage and good prognosis. Br J Cancer, 1996. 74(5): p. 773-9. 50. Tang, X.X., A.E. Evans, H. Zhao, A. Cnaan, G.M. Brodeur, and N. Ikegaki, Association among EPHB2, TrkA, and MYCN expression in low-stage neuroblastomas. Med Pediatr Oncol, 2001. 36(1): p. 80-2. 51. Cohn, S.L., A.D. Pearson, W.B. London, T. Monclair, P.F. Ambros, G.M. Brodeur, A. Faldum, B. Hero, T. Iehara, D. Machin, V. Mosseri, T. Simon, A. Garaventa, V. Castel, and K.K. Matthay, The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol, 2009. 27(2): p. 289-97. 52. Kembhavi, S.A., S. Shah, V. Rangarajan, S. Qureshi, P. Popat, and P. Kurkure, Imaging in neuroblastoma: An update. Indian J Radiol Imaging, 2015. 25(2): p. 129-36. 53. Strother, D.R., W.B. London, M.L. Schmidt, G.M. Brodeur, H. Shimada, P. Thorner, M.H. Collins, E. Tagge, S. Adkins, C.P. Reynolds, K. Murray, R.S. Lavey, K.K. Matthay, R. Castleberry, J.M. Maris, and S.L. Cohn, Outcome after surgery alone or with restricted use of chemotherapy for patients with low-risk neuroblastoma: results of Children's Oncology Group study P9641. J Clin Oncol, 2012. 30(15): p. 1842-8. 54. Baker, D.L., M.L. Schmidt, S.L. Cohn, J.M. Maris, W.B. London, A. Buxton, D. Stram, R.P. Castleberry, H. Shimada, A. Sandler, R.C. Shamberger, A.T. Look, C.P. Reynolds, R.C. Seeger, and K.K. Matthay, Outcome after reduced chemotherapy for intermediate-risk neuroblastoma. N Engl J Med, 2010. 363(14): p. 1313-23. 55. team, T.A.C.S.m.a.e.c. Survival Rates for Neuroblastoma Based on Risk Groups. Date Last Revised: Jan22, 2016; Available from: http://www.cancer.org/cancer/neuroblastoma/detection-diagnosis-staging/survival-rates.html. 56. Winter, J., S. Jung, S. Keller, R.I. Gregory, and S. Diederichs, Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol, 2009. 11(3): p. 228-34. 57. He, L. and G.J. Hannon, MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet, 2004. 5(7): p. 522-31. 58. Kim, V.N., MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol, 2005. 6(5): p. 376-85. 59. Bartel, D.P., MicroRNAs: target recognition and regulatory functions. Cell, 2009. 136(2): p. 215-33. 60. Lee, R.C., R.L. Feinbaum, and V. Ambros, The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell, 1993. 75(5): p. 843-54. 61. Bernstein, E., S.Y. Kim, M.A. Carmell, E.P. Murchison, H. Alcorn, M.Z. Li, A.A. Mills, S.J. Elledge, K.V. Anderson, and G.J. Hannon, Dicer is essential for mouse development. Nat Genet, 2003. 35(3): p. 215-7. 62. Wang, Y., R. Medvid, C. Melton, R. Jaenisch, and R. Blelloch, DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal. Nat Genet, 2007. 39(3): p. 380-5. 63. Liu, J., J. Githinji, B. McLaughlin, K. Wilczek, and J. Nolta, Role of miRNAs in neuronal differentiation from human embryonic stem cell-derived neural stem cells. Stem Cell Rev, 2012. 8(4): p. 1129-37. 64. Xu, C., Y. Lu, Z. Pan, W. Chu, X. Luo, H. Lin, J. Xiao, H. Shan, Z. Wang, and B. Yang, The muscle-specific microRNAs miR-1 and miR-133 produce opposing effects on apoptosis by targeting HSP60, HSP70 and caspase-9 in cardiomyocytes. J Cell Sci, 2007. 120(Pt 17): p. 3045-52. 65. Sayed, D. and M. Abdellatif, MicroRNAs in development and disease. Physiol Rev, 2011. 91(3): p. 827-87. 66. Cordes, K.R. and D. Srivastava, MicroRNA regulation of cardiovascular development. Circ Res, 2009. 104(6): p. 724-32. 67. Esquela-Kerscher, A. and F.J. Slack, Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer, 2006. 6(4): p. 259-69. 68. Michael, M.Z., O.C. SM, N.G. van Holst Pellekaan, G.P. Young, and R.J. James, Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res, 2003. 1(12): p. 882-91. 69. Iorio, M.V., M. Ferracin, C.G. Liu, A. Veronese, R. Spizzo, S. Sabbioni, E. Magri, M. Pedriali, M. Fabbri, M. Campiglio, S. Menard, J.P. Palazzo, A. Rosenberg, P. Musiani, S. Volinia, I. Nenci, G.A. Calin, P. Querzoli, M. Negrini, and C.M. Croce, MicroRNA gene expression deregulation in human breast cancer. Cancer Res, 2005. 65(16): p. 7065-70. 70. Ciafre, S.A., S. Galardi, A. Mangiola, M. Ferracin, C.G. Liu, G. Sabatino, M. Negrini, G. Maira, C.M. Croce, and M.G. Farace, Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun, 2005. 334(4): p. 1351-8. 71. Bray, I., K. Bryan, S. Prenter, P.G. Buckley, N.H. Foley, D.M. Murphy, L. Alcock, P. Mestdagh, J. Vandesompele, F. Speleman, W.B. London, P.W. McGrady, D.G. Higgins, A. O'Meara, M. O'Sullivan, and R.L. Stallings, Widespread dysregulation of MiRNAs by MYCN amplification and chromosomal imbalances in neuroblastoma: association of miRNA expression with survival. PLoS One, 2009. 4(11): p. e7850. 72. Chang, T.C., D. Yu, Y.S. Lee, E.A. Wentzel, D.E. Arking, K.M. West, C.V. Dang, A. Thomas-Tikhonenko, and J.T. Mendell, Widespread microRNA repression by Myc contributes to tumorigenesis. Nat Genet, 2008. 40(1): p. 43-50. 73. Lodrini, M., I. Oehme, C. Schroeder, T. Milde, M.C. Schier, A. Kopp-Schneider, J.H. Schulte, M. Fischer, K. De Preter, F. Pattyn, M. Castoldi, M.U. Muckenthaler, A.E. Kulozik, F. Westermann, O. Witt, and H.E. Deubzer, MYCN and HDAC2 cooperate to repress miR-183 signaling in neuroblastoma. Nucleic Acids Res, 2013. 41(12): p. 6018-33. 74. Loven, J., N. Zinin, T. Wahlstrom, I. Muller, P. Brodin, E. Fredlund, U. Ribacke, A. Pivarcsi, S. Pahlman, and M. Henriksson, MYCN-regulated microRNAs repress estrogen receptor-alpha (ESR1) expression and neuronal differentiation in human neuroblastoma. Proc Natl Acad Sci U S A, 2010. 107(4): p. 1553-8. 75. Schulte, J.H., S. Horn, T. Otto, B. Samans, L.C. Heukamp, U.C. Eilers, M. Krause, K. Astrahantseff, L. Klein-Hitpass, R. Buettner, A. Schramm, H. Christiansen, M. Eilers, A. Eggert, and B. Berwanger, MYCN regulates oncogenic MicroRNAs in neuroblastoma. Int J Cancer, 2008. 122(3): p. 699-704. 76. Ma, L., J. Young, H. Prabhala, E. Pan, P. Mestdagh, D. Muth, J. Teruya-Feldstein, F. Reinhardt, T.T. Onder, S. Valastyan, F. Westermann, F. Speleman, J. Vandesompele, and R.A. Weinberg, miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol, 2010. 12(3): p. 247-56. 77. Buechner, J., E. Tomte, B.H. Haug, J.R. Henriksen, C. Lokke, T. Flaegstad, and C. Einvik, Tumour-suppressor microRNAs let-7 and mir-101 target the proto-oncogene MYCN and inhibit cell proliferation in MYCN-amplified neuroblastoma. Br J Cancer, 2011. 105(2): p. 296-303. 78. Zaragosi, L.E., B. Wdziekonski, K.L. Brigand, P. Villageois, B. Mari, R. Waldmann, C. Dani, and P. Barbry, Small RNA sequencing reveals miR-642a-3p as a novel adipocyte-specific microRNA and miR-30 as a key regulator of human adipogenesis. Genome Biol, 2011. 12(7): p. R64. 79. Wu, Z.H., K.H. Huang, K. Liu, G.T. Wang, and Q. Sun, DGCR5 induces osteogenic differentiation by up-regulating Runx2 through miR-30d-5p. Biochem Biophys Res Commun, 2018. 505(2): p. 426-431. 80. Filios, S.R. and A. Shalev, beta-Cell MicroRNAs: Small but Powerful. Diabetes, 2015. 64(11): p. 3631-44. 81. Osmai, M., Y. Osmai, C.H. Bang-Berthelsen, E.M. Pallesen, A.L. Vestergaard, G.W. Novotny, F. Pociot, and T. Mandrup-Poulsen, MicroRNAs as regulators of beta-cell function and dysfunction. Diabetes Metab Res Rev, 2016. 32(4): p. 334-49. 82. Chen, D., W. Guo, Z. Qiu, Q. Wang, Y. Li, L. Liang, L. Liu, S. Huang, Y. Zhao, and X. He, MicroRNA-30d-5p inhibits tumour cell proliferation and motility by directly targeting CCNE2 in non-small cell lung cancer. Cancer Lett, 2015. 362(2): p. 208-17. 83. Ye, Z., L. Zhao, J. Li, W. Chen, and X. Li, miR-30d Blocked Transforming Growth Factor beta1-Induced Epithelial-Mesenchymal Transition by Targeting Snail in Ovarian Cancer Cells. Int J Gynecol Cancer, 2015. 25(9): p. 1574-81. 84. Zhu, B., H. Chen, X. Zhang, Y. Pan, R. Jing, L. Shen, X. Wang, S. Ju, C. Jin, and H. Cong, Serum miR-30d as a novel biomarker for multiple myeloma and its antitumor role in U266 cells through the targeting of the MTDH/PI3K/Akt signaling pathway. Int J Oncol, 2018. 53(5): p. 2131-2144. 85. Sempere, L.F., S. Freemantle, I. Pitha-Rowe, E. Moss, E. Dmitrovsky, and V. Ambros, Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol, 2004. 5(3): p. R13. 86. Takane, K., K. Fujishima, Y. Watanabe, A. Sato, N. Saito, M. Tomita, and A. Kanai, Computational prediction and experimental validation of evolutionarily conserved microRNA target genes in bilaterian animals. BMC Genomics, 2010. 11: p. 101. 87. Caygill, E.E. and L.A. Johnston, Temporal regulation of metamorphic processes in Drosophila by the let-7 and miR-125 heterochronic microRNAs. Curr Biol, 2008. 18(13): p. 943-50. 88. Le, M.T., C. Teh, N. Shyh-Chang, H. Xie, B. Zhou, V. Korzh, H.F. Lodish, and B. Lim, MicroRNA-125b is a novel negative regulator of p53. Genes Dev, 2009. 23(7): p. 862-76. 89. Liang, L., C.M. Wong, Q. Ying, D.N. Fan, S. Huang, J. Ding, J. Yao, M. Yan, J. Li, M. Yao, I.O. Ng, and X. He, MicroRNA-125b suppressesed human liver cancer cell proliferation and metastasis by directly targeting oncogene LIN28B2. Hepatology, 2010. 52(5): p. 1731-40. 90. Nam, E.J., H. Yoon, S.W. Kim, H. Kim, Y.T. Kim, J.H. Kim, J.W. Kim, and S. Kim, MicroRNA expression profiles in serous ovarian carcinoma. Clin Cancer Res, 2008. 14(9): p. 2690-5. 91. Hui, A.B., M. Lenarduzzi, T. Krushel, L. Waldron, M. Pintilie, W. Shi, B. Perez-Ordonez, I. Jurisica, B. O'Sullivan, J. Waldron, P. Gullane, B. Cummings, and F.F. Liu, Comprehensive MicroRNA profiling for head and neck squamous cell carcinomas. Clin Cancer Res, 2010. 16(4): p. 1129-39. 92. Visone, R., P. Pallante, A. Vecchione, R. Cirombella, M. Ferracin, A. Ferraro, S. Volinia, S. Coluzzi, V. Leone, E. Borbone, C.G. Liu, F. Petrocca, G. Troncone, G.A. Calin, A. Scarpa, C. Colato, G. Tallini, M. Santoro, C.M. Croce, and A. Fusco, Specific microRNAs are downregulated in human thyroid anaplastic carcinomas. Oncogene, 2007. 26(54): p. 7590-5. 93. Pinto, M.T., L.D. Nicolete, E.S. Rodrigues, P.V. Palma, M.D. Orellana, S. Kashima, and D.T. Covas, Overexpression of hsa-miR-125b during osteoblastic differentiation does not influence levels of Runx2, osteopontin, and ALPL gene expression. Braz J Med Biol Res, 2013. 46(8): p. 676-80. 94. Amir, S., A.H. Ma, X.B. Shi, L. Xue, H.J. Kung, and R.W. Devere White, Oncomir miR-125b suppresses p14(ARF) to modulate p53-dependent and p53-independent apoptosis in prostate cancer. PLoS One, 2013. 8(4): p. e61064. 95. Wu, N., L. Xiao, X. Zhao, J. Zhao, J. Wang, F. Wang, S. Cao, and X. Lin, miR-125b regulates the proliferation of glioblastoma stem cells by targeting E2F2. FEBS Lett, 2012. 586(21): p. 3831-9. 96. Bhattacharjya, S., S. Nath, J. Ghose, G.P. Maiti, N. Biswas, S. Bandyopadhyay, C.K. Panda, N.P. Bhattacharyya, and S. Roychoudhury, miR-125b promotes cell death by targeting spindle assembly checkpoint gene MAD1 and modulating mitotic progression. Cell Death Differ, 2013. 20(3): p. 430-42. 97. Cui, F., X. Li, X. Zhu, L. Huang, Y. Huang, C. Mao, Q. Yan, J. Zhu, W. Zhao, and H. Shi, MiR-125b inhibits tumor growth and promotes apoptosis of cervical cancer cells by targeting phosphoinositide 3-kinase catalytic subunit delta. Cell Physiol Biochem, 2012. 30(5): p. 1310-8. 98. Feliciano, A., J. Castellvi, A. Artero-Castro, J.A. Leal, C. Romagosa, J. Hernandez-Losa, V. Peg, A. Fabra, F. Vidal, H. Kondoh, Y.C.S. Ramon, and M.E. Lleonart, miR-125b acts as a tumor suppressor in breast tumorigenesis via its novel direct targets ENPEP, CK2-alpha, CCNJ, and MEGF9. PLoS One, 2013. 8(10): p. e76247. 99. Kappelmann, M., S. Kuphal, G. Meister, L. Vardimon, and A.K. Bosserhoff, MicroRNA miR-125b controls melanoma progression by direct regulation of c-Jun protein expression. Oncogene, 2013. 32(24): p. 2984-91. 100. Shiiba, M., K. Shinozuka, K. Saito, K. Fushimi, A. Kasamatsu, K. Ogawara, K. Uzawa, H. Ito, Y. Takiguchi, and H. Tanzawa, MicroRNA-125b regulates proliferation and radioresistance of oral squamous cell carcinoma. Br J Cancer, 2013. 108(9): p. 1817-21. 101. Xu, N., L. Zhang, F. Meisgen, M. Harada, J. Heilborn, B. Homey, D. Grander, M. Stahle, E. Sonkoly, and A. Pivarcsi, MicroRNA-125b down-regulates matrix metallopeptidase 13 and inhibits cutaneous squamous cell carcinoma cell proliferation, migration, and invasion. J Biol Chem, 2012. 287(35): p. 29899-908. 102. Nakata, A., H. Shinagawa, and M. Amemura, Cloning of alkaline phosphatase isozyme gene (iap) of Escherichia coli. Gene, 1982. 19(3): p. 313-9. 103. Jinek, M., K. Chylinski, I. Fonfara, M. Hauer, J.A. Doudna, and E. Charpentier, A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science, 2012. 337(6096): p. 816-21. 104. Sapranauskas, R., G. Gasiunas, C. Fremaux, R. Barrangou, P. Horvath, and V. Siksnys, The Streptococcus thermophilus CRISPR/Cas system provides immunity in Escherichia coli. Nucleic Acids Res, 2011. 39(21): p. 9275-82. 105. Deltcheva, E., K. Chylinski, C.M. Sharma, K. Gonzales, Y. Chao, Z.A. Pirzada, M.R. Eckert, J. Vogel, and E. Charpentier, CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. Nature, 2011. 471(7340): p. 602-7. 106. Marraffini, L.A. and E.J. Sontheimer, Self versus non-self discrimination during CRISPR RNA-directed immunity. Nature, 2010. 463(7280): p. 568-71. 107. Perez, E.E., J. Wang, J.C. Miller, Y. Jouvenot, K.A. Kim, O. Liu, N. Wang, G. Lee, V.V. Bartsevich, Y.L. Lee, D.Y. Guschin, I. Rupniewski, A.J. Waite, C. Carpenito, R.G. Carroll, J.S. Orange, F.D. Urnov, E.J. Rebar, D. Ando, P.D. Gregory, J.L. Riley, M.C. Holmes, and C.H. June, Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nat Biotechnol, 2008. 26(7): p. 808-16. 108. Saleh-Gohari, N. and T. Helleday, Conservative homologous recombination preferentially repairs DNA double-strand breaks in the S phase of the cell cycle in human cells. Nucleic Acids Res, 2004. 32(12): p. 3683-8. 109. Chen, F., S.M. Pruett-Miller, Y. Huang, M. Gjoka, K. Duda, J. Taunton, T.N. Collingwood, M. Frodin, and G.D. Davis, High-frequency genome editing using ssDNA oligonucleotides with zinc-finger nucleases. Nat Methods, 2011. 8(9): p. 753-5. 110. Makarova, K.S., D.H. Haft, R. Barrangou, S.J. Brouns, E. Charpentier, P. Horvath, S. Moineau, F.J. Mojica, Y.I. Wolf, A.F. Yakunin, J. van der Oost, and E.V. Koonin, Evolution and classification of the CRISPR-Cas systems. Nat Rev Microbiol, 2011. 9(6): p. 467-77. 111. Marraffini, L.A. and E.J. Sontheimer, CRISPR interference limits horizontal gene transfer in staphylococci by targeting DNA. Science, 2008. 322(5909): p. 1843-5. 112. Hale, C.R., S. Majumdar, J. Elmore, N. Pfister, M. Compton, S. Olson, A.M. Resch, C.V. Glover, 3rd, B.R. Graveley, R.M. Terns, and M.P. Terns, Essential features and rational design of CRISPR RNAs that function with the Cas RAMP module complex to cleave RNAs. Mol Cell, 2012. 45(3): p. 292-302. 113. Makarova, K.S., L. Aravind, Y.I. Wolf, and E.V. Koonin, Unification of Cas protein families and a simple scenario for the origin and evolution of CRISPR-Cas systems. Biol Direct, 2011. 6: p. 38. 114. Gupta, R.M. and K. Musunuru, Expanding the genetic editing tool kit: ZFNs, TALENs, and CRISPR-Cas9. J Clin Invest, 2014. 124(10): p. 4154-61. 115. Ding, Q., S.N. Regan, Y. Xia, L.A. Oostrom, C.A. Cowan, and K. Musunuru, Enhanced efficiency of human pluripotent stem cell genome editing through replacing TALENs with CRISPRs. Cell Stem Cell, 2013. 12(4): p. 393-4. 116. Guilinger, J.P., D.B. Thompson, and D.R. Liu, Fusion of catalytically inactive Cas9 to FokI nuclease improves the specificity of genome modification. Nat Biotechnol, 2014. 32(6): p. 577-582. 117. Chen, X., F. Xu, C. Zhu, J. Ji, X. Zhou, X. Feng, and S. Guang, Dual sgRNA-directed gene knockout using CRISPR/Cas9 technology in Caenorhabditis elegans. Sci Rep, 2014. 4: p. 7581. 118. Aminzadeh, S., S. Vidali, W. Sperl, B. Kofler, and R.G. Feichtinger, Energy metabolism in neuroblastoma and Wilms tumor. Transl Pediatr, 2015. 4(1): p. 20-32. 119. 國立臺灣大學醫學檢驗暨生物技術學研究所張勝凱博士論文 https://hdl.handle.net/11296/z234v4 120. 國立臺灣大學醫學檢驗暨生物技術學研究所李文博碩士論文 121. Li, Y., A.I. Park, H. Mou, C. Colpan, A. Bizhanova, E. Akama-Garren, N. Joshi, E.A. Hendrickson, D. Feldser, H. Yin, D.G. Anderson, T. Jacks, Z. Weng, and W. Xue, A versatile reporter system for CRISPR-mediated chromosomal rearrangements. Genome Biol, 2015. 16: p. 111. 122. Song, Y., L. Yuan, Y. Wang, M. Chen, J. Deng, Q. Lv, T. Sui, Z. Li, and L. Lai, Efficient dual sgRNA-directed large gene deletion in rabbit with CRISPR/Cas9 system. Cell Mol Life Sci, 2016. 73(15): p. 2959-68. 123. Ran, F.A., P.D. Hsu, J. Wright, V. Agarwala, D.A. Scott, and F. Zhang, Genome engineering using the CRISPR-Cas9 system. Nat Protoc, 2013. 8(11): p. 2281-2308. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78636 | - |
| dc.description.abstract | 神經母細胞瘤 (Neuroblastoma, NB)是常見的兒童顱外惡性腫瘤，約造成兒童癌症死亡的12%；根據其組織特徵、轉錄體和分化的特性，被認為是由於腎上腺交感神經前驅細胞異常分化增生所導致。NB為異質性很高的腫瘤，約20~25% 的NB病人腫瘤具有MYCN基因增幅，而MYCN是否發生基因增幅為目前所知NB最重要的預後不良因子。從大規模基因分析數據中可得知高度惡性NB基因外顯子突變率低，且較少有反覆出現的突變基因，表示在基因突變外的異常基因調控網絡對於NB發展以及進程上扮演重要角色。目前對於高度惡性的NB病患是以高劑量的化療/放療/手術切除等多管道方式進行治療，但在半數病患治療成效仍不甚理想。
微核醣核酸mircoRNA為長約20~23個核苷酸短片段、內生性的單股核糖核酸，主要功能為透過轉譯後調控抑制標的基因的表現。過去研究發現microRNA的表現與多種癌症的形成相關，且在不同系統癌症中可能扮演抑癌因子或致癌因子不同角色。我們先前系列研究中發現:在NB病患中腫瘤的miR-125b, miR-30d低表現量與較差的臨床預後相關。且在MYCN amplified NB細胞株SKNDZ, SKNBE中miR-125b, miR-30d 的表現量低於MYCN non-amplified 細胞株SKNSH, SH-SY5Y。過去在SKNDZ、SKNBE細胞株中利用慢病毒轉導過表現miR-125b, miR-30d後觀察到細胞增生及非貼附生長受抑制、遷移及侵襲能力降低，並且細胞內的ATP產生增高，暗示了miR30d和miR125b在MYCN-A NB扮演抑癌因子的角色並可能影響細胞內能量代謝。可惜因技術困難尚未能成功有效抑制miRNA的表現以確證miR-125b與miR-30d表現受抑制下是否影響NB腫瘤細胞的惡性表現型。 CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins)是一種新興的基因剪輯工具，可以高特異性的在活細胞中編輯我們有興趣的基因; 在本研究中我們成功利用雙gRNA引導的CRISPR/Cas9技術在SH-SY5Y NB細胞株中對MIR125B1或MIR30D基因座進行編修，且成功篩選出標的細胞，得以有效抑制miR-125b或miR-30d表現。在二種經編修的標的細胞中均發現細胞生長速度上升、細胞非貼附生長能力上升、遷移能力上升以及ATP生成量減少等現象，確證miR-125b, miR-30d在MYCN-NA NB腫瘤中亦扮演tumor suppressor的角色並可能涉及細胞中的能量代謝。本研究並針對gRNA可能引發的脫靶效應進行探查，結果並未發現脫靶效應發生。MIR125B1及MIR30D標的細胞的產製將可運用於後續探索miR-125b, miR-30d在NB腫瘤生成中的調控網絡以及下游影響的基因，並找尋惡性NB可能的治療標的。 | zh_TW |
| dc.description.abstract | Neuroblastoma (NB) is a common extracranial malignant tumor in children, accounting for about 12% of pediatric cancer mortality. It is characterized by abnormal differentiation and proliferation of adrenal sympathetic nerve precursor cells. NB is a highly heterogeneous in clinical settings. About 20-25% of NB patients have MYCN-amplification in the tumor, which is currently known as the most important prognostic factor of NB’s disease progression. A large-scaled genetic study on high risk NBs revealed a low median exonic mutation and notably few recurrent mutated genes, indicating aberrant gene regulation network beyond genetic mutation plays an important role in tumorgenesis and tumor progression in NB. Parients with high-risk NB are currently treated with high-dose chemotherapies/ radiotherapy and surgical resection, however, the treatment outcome remained poor in half of these patients.
MircoRNAs are endogenous small RNAs of 20~23 nucleotides that can transcriptionally repress their target genes. Previous reports showed that microRNA can act as a tumor suppressor or be oncogenic in different context. We previously showed lower miR-125b or miR-30d expression in primary NB tumors correlated to adverse clinical outcome. Among NB cell lines, miR125b and miR-30d expression are lower in MYCN-amplified (MYCN-A) SKNDZ and SKNBE than in MYCN-non amplified (MYCN-NA) SKNSH and SH-SY5Y. Enforced overexpression of miR-125b or miR-30d in SKNDZ and SKNBE cells inhibited cellular proliferation, reduced anchorage-independent cell growth, migration and invasion ability while increased glucose uptake and ATP production. These data indicate that miR125b and miR-30d play as tumor suppressors in NB tumors and may be involved in the regulation of energy metabolism. However, we have not yet confirmed the tumor suppressive effects of these two microRNAs in the experimental settings with reduced miR-125b, miR-30d expression in NB cells, due to problems encountered in anti-miR technique. CRISPR/Cas (clustered regularly interspaced short palindromic repeats/ CRISPR-associated proteins) system is a newly emerged gene editing tool used for specific gene alteration in living cells. We successfully targeted MIR125B1, MIR30D in MYCN-NA SH-SY5Y cell line using dual gRNA-guided CRISPR/ Cas9 system and obtained gene-targeted cell clones with marked miR-125b or miR-30d repression. These clones showed enhanced cellular proliferation, anchorage-independent cell growth, migration ability and decreased ATP production, as compared to the control cells, which verify the hypothesis that miR-125b and miR-30d play as tumor suppressors in NB tumors and is involved in the regulation of energy metabolism. We also used RGEN software to predict off-target sites of each gRNA and PCR/sequecing to rule out the possibility of off-target damage of the tested cells. In the future, we will continue to explore the gene regulatory network of miR-125b and miR-30d in tumorigenesis and its downstream regulatory genes. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:08:52Z (GMT). No. of bitstreams: 1 ntu-108-R05424022-1.pdf: 4360917 bytes, checksum: 1f13cb5f5725eba987d02a2a73bff4b1 (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | ABSTRACT 2
摘要 4 縮寫表 6 目錄 7 圖表目錄 10 附錄目錄 11 第一章 緒論 12 1.1 神經母細胞瘤 12 1.1.1 神經母細胞瘤簡介 12 1.1.2 神經母細胞瘤致病機轉 12 1.1.3 神經母細胞瘤臨床表現 13 1.1.4 神經母細胞瘤臨床疾病診斷與分期 14 1.1.5 神經母細胞瘤病理特徵與分類 16 1.1.6 神經母細胞瘤分子標記及預後指標 17 1.1.7 神經母細胞瘤治療方針 19 1.2 微核糖核酸 20 1.2.1 微核醣核酸簡介 20 1.2.2 微核糖核酸生理功能及生理意義 21 1.2.3 微核糖核酸在癌症中扮演的角色 22 1.2.4 微核糖核酸-30d 23 1.2.5 微核糖核酸-125b 24 1.3 CRISPR/Cas9 25 1.3.1 CRIPSR/Cas系統簡介 25 1.3.2 CRISPR/Cas系統的分類 26 1.3.3 CRISPR/Cas9優缺點 28 1.4 瓦氏效應（Warburg effect） 29 1.5 研究動機與研究假說 29 第二章 研究目的與實驗設計 31 2.1 研究目的 31 2.2 實驗設計與架構 31 2.2.1 製備miR-125b1/miR-30d抑制之MYCN-NA細胞株 31 2.2.2 MiR-30d, miR-125b在MYCN-NA細胞中的抑癌能力分析 31 2.2.3 脫靶效應之探查 32 第三章 材料與方法 33 3.1 實驗材料 33 3.1.1 細胞株 33 3.1.2 試劑試藥 33 3.1.3 試劑套組 34 3.1.5 溶液試劑配方 34 3.1.6 實驗儀器 35 3.1.7 CRISPR質體與載體(附錄六) 35 3.1.8 gRNA靶點序列及引子(primer): 用於構築CRISPR/CAS9載體 36 3.1.9 miR-30d, miR-125b引子序列 (檢測gRNA/CRISPR-Cas9質體, screening PCR) 36 3.1.10 MIR-30D 預測脫靶位點基因表及檢測用引子 37 3.1.11 MIR125B1 預測脫靶位點基因及檢測用引子 39 3.1.12 分析軟體與網路工具 39 3.2 實驗方法 41 3.2.1 建立gRNA/CRISPR-Cas9質體(使用pZG22C02/RGN8 cloning 套組)(附錄六) 41 3.2.2 建立miR-125b1或miR-30d編輯之SH-SY5Y細胞 41 3.2.3 解凍細胞、繼代培養 42 3.2.4 非貼附生長能力分析（anchorage-independent growth ability assay） 42 3.2.5 細胞遷移試驗（Migration assay）（Wound healing assay） 43 3.2.6 訊息核醣核酸/微核醣核酸相對表現量（mRNA/miRNA relative expression） 43 3.2.7 三磷酸腺苷產量試驗（ATP production assay） 45 3.2.8 核酸定序 46 3.2.9 數據統計分析（Data statistics） 46 第四章 實驗結果 47 4.1 利用雙gRNA進行CRISPR/Cas9基因編輯製備miR-30d；miR-125b抑制的SH-SY5Y細胞株 47 4.2 微核糖核酸MIR125B1剔除剪輯細胞株其miR-125b表現量確實降低 47 4.3 MIR30D剔除細胞株其miR-30d表現量確實降低 47 4.4 SH-SY5Y於NB細胞株中抑制miR-125b後之細胞表徵分析 48 4.4.1 SH-SY5Y抑制miR-125b後表現細胞形態的變化 48 4.4.2 抑制miR-125b表現促進SY5Y細胞生長 48 4.4.3 抑制miR-125b 表現促進NB細胞遷徙能力 49 4.4.4 抑制miR125b表現促進SY5Y細胞非貼附生長能力 49 4.4.5 抑制miR-125表現減低SY5Y細胞ATP生成能力 49 4.5 於SH-SY5Y NB細胞株中抑制miR-30d後之細胞表徵分析 49 4.5.1 SH-SY5Y細胞抑制miR-30d表現細胞形態的變化 50 4.5.2 抑制miR-30d表現促進SY5Y細胞生長 50 4.5.3 抑制miR-30d表現促進NB細胞遷徙能力 50 4.5.4 抑制miR-30d表現促進SY5Y細胞非貼附生長能力 50 4.5.5 抑制miR-30d表現減低SY5Y細胞ATP生成能力 51 4.6 分析脫靶效應(off-target effect)可能所在的位點 51 4.7 以TA克隆法探討miR-125b剪輯標的細胞確切之染色體修補情形 52 第五章 討論 54 參考文獻 59 | |
| dc.language.iso | zh-TW | |
| dc.title | 在SH-SY5Y細胞中利用CRISPR/CAS9技術探討特定微核醣核酸在神經母細胞瘤細胞中的作用 | zh_TW |
| dc.title | Investigating the effects of specific microRNAs in neuroblastoma using CRISPR/CAS9-mediated gene targeting in SH-SY5Y cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 107-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 周獻堂,黃呈彥,林亮音,歐大諒 | |
| dc.subject.keyword | 神經母細胞瘤,微核醣核酸,抑癌因子,CRISPR/Cas9基因編輯技術, | zh_TW |
| dc.subject.keyword | neuroblastoma,microRNA,tumor suppressor,CRISPR/Cas9 system, | en |
| dc.relation.page | 101 | |
| dc.identifier.doi | 10.6342/NTU201903306 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2019-08-13 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 醫學檢驗暨生物技術學研究所 | zh_TW |
| 顯示於系所單位： | 醫學檢驗暨生物技術學系 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-108-R05424022-1.pdf 目前未授權公開取用 | 4.26 MB | Adobe PDF |
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