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  1. NTU Theses and Dissertations Repository
  2. 醫學院
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請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/44146
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor林泰元
dc.contributor.authorMei-Fang Chiuen
dc.contributor.author邱美芳zh_TW
dc.date.accessioned2021-06-15T02:42:00Z-
dc.date.available2014-09-15
dc.date.copyright2009-09-15
dc.date.issued2009
dc.date.submitted2009-08-11
dc.identifier.citationAkao, Y., Y. Nakagawa, et al. (2007). 'Downregulation of microRNAs-143 and -145 in B-cell malignancies.' Cancer Sci 98(12): 1914-20.
Ambros, V. (2004). 'The functions of animal microRNAs.' Nature 431(7006): 350-5.
Ayanoglou, C. M. and C. Lesty (1999). 'Cyclosporin A-induced gingival overgrowth in the rat: a histological, ultrastructural and histomorphometric evaluation.' J Periodontal Res 34(1): 7-15.
Bartel, D. P. (2004). 'MicroRNAs: genomics, biogenesis, mechanism, and function.' Cell 116(2): 281-97.
Bartel, D. P. (2009). 'MicroRNAs: target recognition and regulatory functions.' Cell 136(2): 215-33.
Borchert, G. M., W. Lanier, et al. (2006). 'RNA polymerase III transcribes human microRNAs.' Nat Struct Mol Biol 13(12): 1097-101.
Bracken, C. P., P. A. Gregory, et al. (2008). 'A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition.' Cancer Res 68(19): 7846-54.
Brennecke, J., A. Stark, et al. (2005). 'Principles of microRNA-target recognition.' PLoS Biol 3(3): e85.
Bueno, M. J., I. Perez de Castro, et al. (2008). 'Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression.' Cancer Cell 13(6): 496-506.
Bushati, N. and S. M. Cohen (2007). 'microRNA functions.' Annu Rev Cell Dev Biol 23: 175-205.
Chen, X., X. Guo, et al. (2009). 'Role of miR-143 targeting KRAS in colorectal tumorigenesis.' Oncogene 28(10): 1385-92.
Christoffersen, N. R., A. Silahtaroglu, et al. (2007). 'miR-200b mediates post-transcriptional repression of ZFHX1B.' RNA 13(8): 1172-8.
Comijn, J., G. Berx, et al. (2001). 'The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion.' Mol Cell 7(6): 1267-78.
Crook, T., J. M. Nicholls, et al. (2000). 'High level expression of deltaN-p63: a mechanism for the inactivation of p53 in undifferentiated nasopharyngeal carcinoma (NPC)?' Oncogene 19(30): 3439-44.
Czech, M. P. (2006). 'MicroRNAs as therapeutic targets.' N Engl J Med 354(11): 1194-5.
Di Como, C. J., M. J. Urist, et al. (2002). 'p63 expression profiles in human normal and tumor tissues.' Clin Cancer Res 8(2): 494-501.
Dohn, M., J. Jiang, et al. (2001). 'Receptor tyrosine kinase EphA2 is regulated by p53-family proteins and induces apoptosis.' Oncogene 20(45): 6503-15.
Dohn, M., S. Zhang, et al. (2001). 'p63alpha and DeltaNp63alpha can induce cell cycle arrest and apoptosis and differentially regulate p53 target genes.' Oncogene 20(25): 3193-205.
Eger, A., K. Aigner, et al. (2005). 'DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells.' Oncogene 24(14): 2375-85.
Esquela-Kerscher, A. and F. J. Slack (2006). 'Oncomirs - microRNAs with a role in cancer.' Nat Rev Cancer 6(4): 259-69.
Fang, J. Y. and B. C. Richardson (2005). 'The MAPK signalling pathways and colorectal cancer.' Lancet Oncol 6(5): 322-7.
Filipowicz, W., S. N. Bhattacharyya, et al. (2008). 'Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?' Nat Rev Genet 9(2): 102-14.
Flores, E. R., K. Y. Tsai, et al. (2002). 'p63 and p73 are required for p53-dependent apoptosis in response to DNA damage.' Nature 416(6880): 560-4.
Gramantieri, L., M. Ferracin, et al. (2007). 'Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma.' Cancer Res 67(13): 6092-9.
Gregory, P. A., A. G. Bert, et al. (2008). 'The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1.' Nat Cell Biol 10(5): 593-601.
Hart, T. C., D. Pallos, et al. (2000). 'Evidence of genetic heterogeneity for hereditary gingival fibromatosis.' J Dent Res 79(10): 1758-64.
Hibi, K., B. Trink, et al. (2000). 'AIS is an oncogene amplified in squamous cell carcinoma.' Proc Natl Acad Sci U S A 97(10): 5462-7.
Hong, H. H., M. I. Uzel, et al. (1999). 'Regulation of lysyl oxidase, collagen, and connective tissue growth factor by TGF-beta1 and detection in human gingiva.' Lab Invest 79(12): 1655-67.
Jones-Rhoades, M. W., D. P. Bartel, et al. (2006). 'MicroRNAS and their regulatory roles in plants.' Annu Rev Plant Biol 57: 19-53.
King, K. E., R. M. Ponnamperuma, et al. (2003). 'deltaNp63alpha functions as both a positive and a negative transcriptional regulator and blocks in vitro differentiation of murine keratinocytes.' Oncogene 22(23): 3635-44.
Koga, F., S. Kawakami, et al. (2003). 'Impaired Delta Np63 expression associates with reduced beta-catenin and aggressive phenotypes of urothelial neoplasms.' Br J Cancer 88(5): 740-7.
Koster, M. I., S. Kim, et al. (2004). 'p63 is the molecular switch for initiation of an epithelial stratification program.' Genes Dev 18(2): 126-31.
Koster, M. I., S. Kim, et al. (2005). 'P63 deficiency: a failure of lineage commitment or stem cell maintenance?' J Investig Dermatol Symp Proc 10(2): 118-23.
Lee, R. C., R. L. Feinbaum, et al. (1993). 'The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.' Cell 75(5): 843-54.
Lee, Y., M. Kim, et al. (2004). 'MicroRNA genes are transcribed by RNA polymerase II.' EMBO J 23(20): 4051-60.
Lena, A. M., R. Shalom-Feuerstein, et al. (2008). 'miR-203 represses 'stemness' by repressing DeltaNp63.' Cell Death Differ 15(7): 1187-95.
Liefer, K. M., M. I. Koster, et al. (2000). 'Down-regulation of p63 is required for epidermal UV-B-induced apoptosis.' Cancer Res 60(15): 4016-20.
Liu, C. G., G. A. Calin, et al. (2004). 'An oligonucleotide microchip for genome-wide microRNA profiling in human and mouse tissues.' Proc Natl Acad Sci U S A 101(26): 9740-4.
Lu, J., G. Getz, et al. (2005). 'MicroRNA expression profiles classify human cancers.' Nature 435(7043): 834-8.
Michael, M. Z., O. C. SM, et al. (2003). 'Reduced accumulation of specific microRNAs in colorectal neoplasia.' Mol Cancer Res 1(12): 882-91.
Mills, A. A., B. Zheng, et al. (1999). 'p63 is a p53 homologue required for limb and epidermal morphogenesis.' Nature 398(6729): 708-13.
Nylander, K., P. J. Coates, et al. (2000). 'Characterization of the expression pattern of p63 alpha and delta Np63 alpha in benign and malignant oral epithelial lesions.' Int J Cancer 87(3): 368-72.
Nylander, K., B. Vojtesek, et al. (2002). 'Differential expression of p63 isoforms in normal tissues and neoplastic cells.' J Pathol 198(4): 417-27.
Okada, Y., M. Osada, et al. (2002). 'p53 gene family p51(p63)-encoded, secondary transactivator p51B(TAp63alpha) occurs without forming an immunoprecipitable complex with MDM2, but responds to genotoxic stress by accumulation.' Exp Cell Res 276(2): 194-200.
Park, S. M., A. B. Gaur, et al. (2008). 'The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2.' Genes Dev 22(7): 894-907.
Parsa, R., A. Yang, et al. (1999). 'Association of p63 with proliferative potential in normal and neoplastic human keratinocytes.' J Invest Dermatol 113(6): 1099-105.
Patturajan, M., S. Nomoto, et al. (2002). 'DeltaNp63 induces beta-catenin nuclear accumulation and signaling.' Cancer Cell 1(4): 369-79.
Pellegrini, G., E. Dellambra, et al. (2001). 'p63 identifies keratinocyte stem cells.' Proc Natl Acad Sci U S A 98(6): 3156-61.
Pillai, R. S. (2005). 'MicroRNA function: multiple mechanisms for a tiny RNA?' RNA 11(12): 1753-61.
Polakis, P. (2000). 'Wnt signaling and cancer.' Genes Dev 14(15): 1837-51.
Reinhart, B. J., F. J. Slack, et al. (2000). 'The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans.' Nature 403(6772): 901-6.
Sachdeva, M., S. Zhu, et al. (2009). 'p53 represses c-Myc through induction of the tumor suppressor miR-145.' Proc Natl Acad Sci U S A 106(9): 3207-12.
Saito, K., S. Mori, et al. (2000). 'Immunolocalizaiton of c-Myc and bcl-2 proto-oncogene products in gingival hyperplasia induced by nifedipine and phenytoin.' J Periodontol 71(1): 44-9.
Sbisa, E., G. Mastropasqua, et al. (2006). 'Connecting p63 to cellular proliferation: the example of the adenosine deaminase target gene.' Cell Cycle 5(2): 205-12.
Senoo, M., F. Pinto, et al. (2007). 'p63 Is essential for the proliferative potential of stem cells in stratified epithelia.' Cell 129(3): 523-36.
Sonkoly, E., T. Wei, et al. (2007). 'MicroRNAs: novel regulators involved in the pathogenesis of Psoriasis?' PLoS ONE 2(7): e610.
Thatcher, E. J., I. Paydar, et al. (2008). 'Regulation of zebrafish fin regeneration by microRNAs.' Proc Natl Acad Sci U S A 105(47): 18384-9.
Trackman, P. C. and A. Kantarci (2004). 'Connective tissue metabolism and gingival overgrowth.' Crit Rev Oral Biol Med 15(3): 165-75.
Truong, A. B., M. Kretz, et al. (2006). 'p63 regulates proliferation and differentiation of developmentally mature keratinocytes.' Genes Dev 20(22): 3185-97.
Vijayasingham, S. M., P. J. Dykes, et al. (1991). 'Phenytoin has little effect on in-vitro models of wound healing.' Br J Dermatol 125(2): 136-9.
Vittek, J., G. G. Gordon, et al. (1983). 'Phenytoin effect on the proliferation of rat oral epithelium is mediated by a hormonal mechanism.' Cell Differ 12(6): 335-9.
Volinia, S., G. A. Calin, et al. (2006). 'A microRNA expression signature of human solid tumors defines cancer gene targets.' Proc Natl Acad Sci U S A 103(7): 2257-61.
Wang, S., C. Bian, et al. (2009). 'miR-145 inhibits breast cancer cell growth through RTKN.' Int J Oncol 34(5): 1461-6.
Winter, J., S. Jung, et al. (2009). 'Many roads to maturity: microRNA biogenesis pathways and their regulation.' Nat Cell Biol 11(3): 228-34.
Xu, N., T. Papagiannakopoulos, et al. (2009). 'MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells.' Cell 137(4): 647-58.
Yang, A., M. Kaghad, et al. (1998). 'p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities.' Mol Cell 2(3): 305-16.
Yang, A. and F. McKeon (2000). 'P63 and P73: P53 mimics, menaces and more.' Nat Rev Mol Cell Biol 1(3): 199-207.
Yang, A., R. Schweitzer, et al. (1999). 'p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development.' Nature 398(6729): 714-8.
Yi, R., M. N. Poy, et al. (2008). 'A skin microRNA promotes differentiation by repressing 'stemness'.' Nature 452(7184): 225-9.
Zamore, P. D. and B. Haley (2005). 'Ribo-gnome: the big world of small RNAs.' Science 309(5740): 1519-24.
Zoeller, J., M. Flentje, et al. (1994). 'Evaluation of AgNOR and Ki-67 antigen as cell kinetic parameters in oral dysplasias and carcinomas.' Anal Cell Pathol 7(1): 77-88.
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/44146-
dc.description.abstract長期服用抗癲癇藥物phenytoin而造成藥物誘發牙齦增生個案於最早於1939年被報導。隨後,免疫抑制劑cyclosporin A和鈣離子阻斷劑nifedipine也被發現會造成牙齦增生。藥物誘發牙齦增生的發生率隨不同藥物而有所不同。大約百分之五十的患者服用phenytoin會造成牙齦增生;使用cyclosporin A和nifedipine而產生這種副作用的比例分別是百分之三十和百分之二十。牙齦增生在病理組織上的改變主要是纖維化或增大的結締組織和增厚的上皮。目前為止,大部分的研究結果指出在結締組織細胞外間質特別是膠原蛋白的堆積在牙齦增生的過程中扮演重要的角色。然而,在牙齦增生中造成上皮細胞增生的機轉仍未明。在這個研究中,我們發現p63這個維持上皮幹細胞的必須因子在先天性和藥物誘發牙齦增生的上皮組織中有過度表現的現象。再者,透過microarray的分析,發現先天性和藥物誘發的牙齦增生組織中有些microRNA (miRNA) 與在正常牙齦組織中表現不同。這些miRNA可能透過作用在p63上而調控角質幹細胞。miRNAs被認為會調控細胞生長、分化、及死亡,而根據這個研究顯示服用藥物而造成牙齦增生的這個副作用可能是透過miRNA調控角質幹細胞而來的。zh_TW
dc.description.abstractDrug-induced gingival overgrowth was first reported in 1939 as a consequence of chronic usage of anti-epileptic drug phenytoin. Later, immunosuppressive drug cyclosporin A and calcium channel blocker nifedipine were observed to cause gingival overgrowth, too. The incidence of gingival overgrowth caused by these three drugs are not the same. Approximately 50 % of patients taking phenytoin are facing with this disturbing side effect while 30 % and 20 % for patients taking cyclosporin A and nifedipine, respectively. Histological change of gingival overgrowth is characterized by fibrotic or expanded connective tissues as well as an enlarged gingival epithelium. So far, many reports have indicated that extracellular matrix accumulation in connective tissue, particularly the collagenous component, played the important roles in gingival overgrowth. However, the pathogenic mechanisms for epithelial cells hyperproliferation of gingival overgrowth were largely unknown. In our recently study, we found that p63, the essential factors for epithelial stem cell maintenance, was overexpressed in epithelium of inherited and phenytoin-induced gingival overgrowth tissue compared with normal gingival tissue. Furthermore, the analysis for microRNA expression profiles of inherited and drug-induced gingival overgrowth by microRNA arrays and real-time PCR indicated that some microRNAs expressed differently between gingival overgrowth tissue and normal gingival tissue. And, these microRNAs might target to p63 and regulate keratinocytes stem cell stemness. It have been reported that microRNAs were well known to regulate cell proliferation, differentiation, and cell death, therefore, our findings suggested that the unwanted side effect of these drugs might be caused through the regulation between microRNAs and keratinocyte stem cell.en
dc.description.provenanceMade available in DSpace on 2021-06-15T02:42:00Z (GMT). No. of bitstreams: 1
ntu-98-R96443015-1.pdf: 3190068 bytes, checksum: 3913de5a18dc16f64d79fe043fee5765 (MD5)
Previous issue date: 2009
en
dc.description.tableofcontents論文口試委員審定書 i
誌謝 ii
ABBREVIATION iii
中文摘要 iv
ABSTRACT v
INTRODUCTION 1
Gingival overgrowth 2
Mechanism 2
p63 3
Isoforms 3
Roles in morphogenesis 4
Roles in tumoregenesis 5
microRNA 6
Biogenesis 7
Mechanism 8
Aim 9
MATERIALS AND METHODS 17
Pateint specimen 18
Cell culture and transfection 18
Immunohistochemistry 18
Quantitative real-time PCR 18
Western blotting 19
Cell cycle analysis 19
RESULTS 21
HE staining of normal gingiva, inherited, and drug-induced gingival overgrowth 22
Expression of ki67 of inherited, drug-induced gingival overgrowth and normal gingival 22
Expression of p63 of inherited, drug-induced gingival overgrowth and normal gingival 23
miRNA microarray of inherited, drug-induced, idiopathic gingival overgrowth gingival 24
microRNAs expression pattern gingival overgrowth 25
p63 expression pattern in SG oral keratinocyte 26
Effect of phenytoin on cell cycle progression in SG oral keratinocyte 26
Effect of miRNAs on p63 expression in SG cells 26
Effect of phenytoin on p63 expression in HaCaT cells 27
Effect of phenytoin on cell cycle progression in HaCaT cells 27
Effect of miRNAs on p63 expression in HaCaT cells 27
Effect of miR-203 on p63 expression and cell cycle progression in HaCaT cells 28
Effect of miR-143 on p63 expression and cell cycle progression in HaCaT cells 28
DISCUSSION 52
CONCLUSION 56
REFERENCE 58
dc.language.isoen
dc.subject角質幹細胞zh_TW
dc.subject微核糖核酸zh_TW
dc.subject牙齦增生zh_TW
dc.subjectgingival overgrowthen
dc.subjectkeratinocyte stem cellen
dc.subjectmicroRNAen
dc.titlemicroRNAs 在牙齦增生之調控角色研究zh_TW
dc.titleThe Study of the Role of microRNAs in the Regulation Gingival Overgrowthen
dc.typeThesis
dc.date.schoolyear97-2
dc.description.degree碩士
dc.contributor.oralexamcommittee劉宏輝,黃彥華
dc.subject.keyword微核糖核酸,牙齦增生,角質幹細胞,zh_TW
dc.subject.keywordmicroRNA,gingival overgrowth,keratinocyte stem cell,en
dc.relation.page62
dc.rights.note有償授權
dc.date.accepted2009-08-11
dc.contributor.author-college醫學院zh_TW
dc.contributor.author-dept藥理學研究所zh_TW
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