(54.236.58.220) 您好!臺灣時間:2021/02/27 18:04
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:蘇欣蘭
研究生(外文):Hsin-Lan Su
論文名稱:miR-486對鼻咽癌的發生所扮演之功能角色
論文名稱(外文):The Functional Role of miR-486 in Nasopharyngeal Carcinoma Tumorigenesis
指導教授:林欽塘林欽塘引用關係
口試日期:2017-07-20
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:病理學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2017
畢業學年度:105
語文別:英文
論文頁數:60
中文關鍵詞:鼻咽癌RECK基因miR-486細胞增殖細胞侵犯
外文關鍵詞:NPC tumorigenesismiR-486reversion-inducing-cysteine-rich protein with kazal motifs (RECK)metastasis suppressor
相關次數:
  • 被引用被引用:0
  • 點閱點閱:44
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
相較於其他癌症,鼻咽癌具有相當高的「地區性」,盛行於中國大陸東南沿海、香港、新加坡、台灣等地,其致病機轉相當複雜。雖然診斷及治療方法不斷進步,但因其發病部位較為隱密,待病患查覺異狀至確診,往往已是晚期,使得預後不良。近期有研究指出Epstein-Barr virus (EBV)與鼻咽癌的惡化有關。在本次研究中發現鼻咽癌細胞株經異體移植(xenografts)得到的同源亞細胞株(sub-cell line),其腫瘤生長力(tumorgenesis)遠大於原細胞株。分析兩細胞株的表現和細胞行為,可得知鼻咽癌亞細胞株在細胞增殖(proliferation)及細胞侵犯(invasion)上具有較強勢的作用。已知microRNA可調控細胞的基因表現,比較兩種細胞株發現在亞細胞株中之hsa-miR-486表現量明顯較高。經由RNA微陣列分析(RNA microarray analysis)發現Reversion-inducing-cysteine-rich protein with kazal motifs (RECK)腫瘤抑制基因會受到miR-486的調節。我們找到RECK基因上miR-486的結合位,將建構好具有miR-486結合位的RECK基因mRNA片斷載體轉染入此二細胞株中,以觀察其對腫瘤發生的能力,並同時進行老鼠活體試驗,從而證實miR-486可抑制RECK基因造成鼻咽癌細胞的腫瘤發生。RECK基因可調控鼻咽癌之生長在之前的SXO-5基因表達之研究中已發現,但與miR-486之關係在鼻咽癌的進展中未曾被發現過,在未來研發中可預期其可能作為分子標靶之治療。
To compare with other cancer disease, nasopharyngeal carcinoma (NPC) often occurs in local region, such as in the southeast coast of the mainland China , Hong Kong, Singapore , and Taiwan. Its pathogenesis is quite complex. Despite advances in diagnosis and treatment , and because of the incidence of the more intimate parts , the abnormal symptoms in patients with perceptible to the diagnosis often is late, resulting in a poor prognosis . Recent researches have pointed out that Epstein-Barr virus (EBV) is one of the reasons that cause nasopharyngeal carcinoma progression. In our laboratory study, we have established a NPC sub-line from one NPC line which was produced from the NPC xenografts. This sub-line showed a higher capacity to induce tumor progression. Analysis of the behavior and phenotype of the original and sub-line showed that NPC sub-line had more higher potential to proliferation, and invasion. Since microRNA can regulate gene expression, we found that the expression of miR-486 has significantly higher in the sub-line. Via RNA microarray analysis of over expressed miR-486, we found that reversion-inducing-cysteine-rich protein with kazal motifs (RECK) gene (a metastasis suppressor) was down regulated by miR-486. Since we have identified that miR-486 binding site presented in RECK gene, therefor we constructed the specific vector expression to transfect in those two cell line. Results showed that miR-486 can regulate RECK gene in two transfected cell lines. At the same time, we have also confirmed the identical results in the in vivo experiment. This is a new finding that RECK gene can regulate NPC progression through miR-486 transfection. In the future for development of NPC treatment, miR-486 may be used as a molecular targeted therapy.
目錄 Table of Contents
口試委員審定書 i
致謝 ii
中文摘要 iii
Abstract iv
List of Figures viii
Introduction 1
1. Nasopharyngeal carcinoma (NPC) 1
2. Etiology of NPC 4
3. microRNA 6
4. miRNA-486 11
5. RECK gene 13
Materials and Methods 17
1. Cell lines 17
2. miRNA 17
3. Extraction of RNA and preparation of cDNA 18
4. Quantitative Time-Lapse Microscopy images 19
5. cDNA Microarray assay 20
6. MTT Assay 21
7. Scratch wound healing assay 21
8. Amplification and Extraction of plasmids 22
9. Mini-plasmid purification 22
10. Invasion assay 23
11. Luciferase assay 24
12. Western Blotting 25
13. Immunohistochemical staining 26
14. In vivo assay of xenograft growth 27
15. Statistical analysis 28
Results 29
1. Cell morphology 29
2. miR-486 regulated NPC cell behavior 29
3. RECK was the miR-486 target gene 30
4. RECK expression was higher in NPC-TW01 than in NPC-TW01N1 cell line 31
5. Immunostaining of RECK protein in NPC biopsy specimens 31
6. Functional analysis of miR-486 in SCID mice bearing NPC xenografts 31
Discussion 33
References 36
Tables 60


List of Figures
Figure 1. Cell Morphology 47
Figure 2. Reduction of cell migration ability in miRNA transfected NPC cell were shown. 48
Figure 3. Differences in proliferation between NPC-TW01 and NPC-TW01N1 ( A) Quantitative Time-Lapse Microscopy images. (B) MTT assay 49
Figure 4. Differences in proliferation between NPC-TW01 transfected miR-486 mimic and negative control ( A) Quantitative Time-Lapse Microscopy images. (B) MTT assay 50
Figure 5. Differences in proliferation between NPC-TW01N1 transfected miR-486 inhibitor and negative control ( A) Quantitative Time-Lapse Microscopy images. (B) MTT assay 51
Figure 6. Differences in invasion ability between NPC-TW01 and NPC-TW01N1 52
Figure 7. Invasion ability is up regulation by miR-486 mimic in NPC-TW01 53
Figure 8. Invasion ability is down regulation by miR-486 inhibitor in NPC-TW01N1 54
Figure 9. Luciferase assay confirm the miR-486 target gene is RECK 55
Figure 10. The expression of RECK protein in NPC-TW01 and NPC-TW01N1 cells. 56
Figure 11. 20 NPC patient’s biopsy specimens were examined by RECK immunostaining. 57
Figure 12. SCID mice bearing NPC-TW01N1 cells after the latter were transfected with miR-486 inhibitor showing marked decrease of xenograft sizes. 58
Adam, F. (2005) microRNA : A Revolution in Gene Expression. Journal of Young Investigators.
Agrawal, N., P. V. Dasaradhi, A. Mohmmed, P. Malhotra, R. K. Bhatnagar & S. K. Mukherjee (2003) RNA interference: biology, mechanism, and applications. Microbiol Mol Biol Rev, 67, 657-85.
Ambros, V. (2004) The functions of animal microRNAs. Nature, 431, 350-5.
Aruoma, O. I., B. Halliwell, B. M. Hoey & J. Butler (1988) The antioxidant action of taurine, hypotaurine and their metabolic precursors. Biochem J. , 256, 251-255.
Axtell, M. J. & D. P. Bartel (2005) Antiquity of microRNAs and their targets in land plants. Plant Cell, 17, 1658-73.
Bartel, D. P. (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116, 281-97.
Brennan, B. (2006) Nasopharyngeal carcinoma. Orphanet J Rare Dis, 1, 23.
Chan, A. T., V. Gregoire, J. L. Lefebvre, L. Licitra, E. P. Hui, S. F. Leung, E. Felip & E.-E.-E. G. W. Group (2012) Nasopharyngeal cancer: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 23 Suppl 7, vii83-5.
Chang, E. T. & H. O. Adami (2006) The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev, 15, 1765-77.
Chang, H. C., C. Y. Cho & W. C. Hung (2007) Downregulation of RECK by promoter methylation correlates with lymph node metastasis in non-small cell lung cancer. Cancer Sci, 98, 169-73.
Chen, H., C. L. Ren, C. X. Han, D. X. Wang, Y. Chen & D. Y. Fu (2015) Expression and Prognostic Value of miR-486-5p in Patients with Gastric Adenocarcinoma. Plos One, 10.
Chen, K. & N. Rajewsky (2007) The evolution of gene regulation by transcription factors and microRNAs. Nat Rev Genet, 8, 93-103.
Chew, M. M., S. Y. Gan, A. S. Khoo & E. L. Tan (2010) Interleukins, laminin and Epstein - Barr virus latent membrane protein 1 (EBV LMP1) promote metastatic phenotype in nasopharyngeal carcinoma. BMC Cancer, 10, 574.
Cho, C. Y., J. H. Wang, H. C. Chang, C. K. Chang & W. C. Hung (2007) Epigenetic inactivation of the metastasis suppressor RECK enhances invasion of human colon cancer cells. Journal of Cellular Physiology, 213, 65-69.
Clark, J. C. M., D. M. Thomas, P. F. M. Choong & C. R. Dass (2007) RECK - a newly discovered inhibitor of metastasis with prognostic significance in multiple forms of cancer. Cancer and Metastasis Reviews, 26, 675-683.
Correa, T. C. S., C. A. Brohem, S. M. B. Winnischofer, L. B. D. S. Cardeal, R. M. Sasahara, S. R. Taboga, M. C. Sogayar & S. S. Maria-Engler (2006) Downregulation of the RECK-tumor and metastasis suppressor gene in glioma invasiveness. Journal of Cellular Biochemistry, 99, 156-167.
Dodd, L. E., S. Sengupta, I. H. Chen, J. A. den Boon, Y. J. Cheng, W. Westra, M. A. Newton, B. F. Mittl, L. McShane, C. J. Chen, P. Ahlquist & A. Hildesheim (2006) Genes involved in DNA repair and nitrosamine metabolism and those located on chromosome 14q32 are dysregulated in nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev, 15, 2216-25.
Dr. N.K. Ganguly , D.-G., Dr. K. Satyanarayana, Dr. V.K. Srivastava (2003) Epidemiological and Etological factors associated with Nasopharyngeal carcinoma. ICMR BULLETIN, 33,NO.9.
Ebhardt, H. A., A. Fedynak & R. P. Fahlman (2010) Naturally occurring variations in sequence length creates microRNA isoforms that differ in argonaute effector complex specificity. Silence, 1, 12.
Echizenya, M., S. Kondo, R. Takahashi, J. Oh, S. Kawashima, H. Kitayama, C. Takahashi & M. Noda (2005) The membrane-anchored MMP-regulator RECK is a target of myogenic regulatory factors. Oncogene, 24, 5850-5857.
Ellwanger, D. C., F. A. Buttner, H. W. Mewes & V. Stumpflen (2011) The sufficient minimal set of miRNA seed types. Bioinformatics, 27, 1346-50.
Friedman, R. C., K. K. Farh, C. B. Burge & D. P. Bartel (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Res, 19, 92-105.
Furumoto, K., S. Arii, A. Mori, H. Furuyama, M. J. G. Rivas, T. Nakao, N. Isobe, T. Murata, C. Takahashi, M. Noda & M. Imamura (2001) RECK gene expression in hepatocellular carcinoma: Correlation with invasion-related clinicopathological factors and its clinical significance. Hepatology, 33, 189-195.
Gallmeier, E., P. C. Hermann, M. T. Mueller, J. G. Machado, A. Ziesch, E. N. De Toni, A. Palagyi, C. Eisen, J. W. Ellwart, J. Rivera, B. Rubio-Viqueira, M. Hidalgo, F. Bunz, B. Goke & C. Heeschen (2011) Inhibition of ataxia telangiectasia- and Rad3-related function abrogates the in vitro and in vivo tumorigenicity of human colon cancer cells through depletion of the CD133(+) tumor-initiating cell fraction. Stem Cells, 29, 418-29.
Gregory, R. I., K. P. Yan, G. Amuthan, T. Chendrimada, B. Doratotaj, N. Cooch & R. Shiekhattar (2004) The Microprocessor complex mediates the genesis of microRNAs. Nature, 432, 235-40.
Griffiths-Jones, S., R. J. Grocock, S. van Dongen, A. Bateman & A. J. Enright (2006) miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res, 34, D140-4.
Gu, Y., X. Zhang, Q. Yang, J. M. Wang, Y. P. He, Z. G. Sun, H. Q. Zhang & J. Wang (2016) Aberrant Placental Villus Expression of miR-486-3p and miR-3074-5p in Recurrent Miscarriage Patients and Uterine Expression of These MicroRNAs during Early Pregnancy in Mice. Gynecologic and Obstetric Investigation, 81, 112-117.
Guo, J. & L. Zou (2006) Correlation of RECK with matrix metalloproteinase-2 in regulation of trophoblast invasion of early pregnancy. J Huazhong Univ Sci Technolog Med Sci, 26, 738-40.
Henrik Hjalgrim, J. F., and Mads Melbye. 2007. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis.
Hermann, P. C., S. L. Huber, T. Herrler, A. Aicher, J. W. Ellwart, M. Guba, C. J. Bruns & C. Heeschen (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell, 1, 313-323.
Hibio, N., K. Hino, E. Shimizu, Y. Nagata & K. Ui-Tei (2012) Stability of miRNA 5 '' terminal and seed regions is correlated with experimentally observed miRNA-mediated silencing efficacy. Scientific Reports, 2.
Hildesheim, A., R. J. Apple, C. J. Chen, S. S. Wang, Y. J. Cheng, W. Klitz, S. J. Mack, I. H. Chen, M. M. Hsu, C. S. Yang, L. A. Brinton, P. H. Levine & H. A. Erlich (2002) Association of HLA class I and II alleles and extended haplotypes with nasopharyngeal carcinoma in Taiwan. J Natl Cancer Inst, 94, 1780-9.
Hildesheim, A. & C. P. Wang (2012) Genetic predisposition factors and nasopharyngeal carcinoma risk: a review of epidemiological association studies, 2000-2011: Rosetta Stone for NPC: genetics, viral infection, and other environmental factors. Semin Cancer Biol, 22, 107-16.
Hitachi, K., M. Nakatani & K. Tsuchida (2014) Myostatin signaling regulates Akt activity via the regulation of miR-486 expression. International Journal of Biochemistry & Cell Biology, 47, 93-103.
Huang, D. Y., Y. T. Lin, P. S. Jan, Y. C. Hwang, S. T. Liang, Y. Peng, C. Y. Huang, H. C. Wu & C. T. Lin (2008) Transcription factor SOX-5 enhances nasopharyngeal carcinoma progression by down-regulating SPARC gene expression. Journal of Pathology, 214, 445-455.
INC, A. 2016. microRNA Sequencing Data Analysis Guideline. Go beyond RNA Arraystar INC.
Inoue, Y., E. Dissanayake, T. Nakano, K. Kudo, S. Misumi, T. Ide, T. Yamamoto, K. Chiba, F. Yamaide, A. Yamaide, T. Arima, M. Tomiita, A. Hoshioka, N. Shimojo & Y. Kohno (2015) Low levels of serum hsa-mir-486 as a biomarker of childhood asthma. Allergy, 70, 22-22.
Jansen, A. M. Patrick, M. Kamsteeg, D. Rodijk-Olthuis, I. M. J. J. Vlijmen-Willems, G. J. Jongh, M. Bergers, Tjabringa, S. Geuranne, Zeeuwen, L. J. M. Patrick & J. Schalkwijk (2009) Expression of the Vanin Gene Family in Normal and Inflamed Human Skin: Induction by Proinflammatory Cytokines. Journal of Investigative Dermatology, 129, 2167-2174.
Jia, W. H., B. J. Feng, Z. L. Xu, X. S. Zhang, P. Huang, L. X. Huang, X. J. Yu, Q. S. Feng, M. H. Yao, Y. Y. Shugart & Y. X. Zeng (2004) Familial risk and clustering of nasopharyngeal carcinoma in Guangdong, China. Cancer, 101, 363-9.
Jia, W. H., Q. H. Pan, H. D. Qin, Y. F. Xu, G. P. Shen, L. Chen, L. Z. Chen, Q. S. Feng, M. H. Hong, Y. X. Zeng & Y. Y. Shugart (2009) A case-control and a family-based association study revealing an association between CYP2E1 polymorphisms and nasopharyngeal carcinoma risk in Cantonese. Carcinogenesis, 30, 2031-6.
Kazal, L. A., D. S. Spicer & R. A. Brahinsky (1948) Isolation of a Crystalline Trypsin Inhibitor-Anticoagulant Protein from Pancreas. Journal of the American Chemical Society, 70, 3034-3040.
Kim, H., K. Kim, M. Lee, S. Seol & H. Kang (2005) Downregulation of MMP by RECK (a novel MMP inhibitor) in osteosarcoma. Ejc Supplements, 3, 347-348.
Kim, Y. J., S. H. Hwang, S. Y. Lee, K. K. Shin, H. H. Cho, Y. C. Bae & J. S. Jung (2012) miR-486-5p Induces Replicative Senescence of Human Adipose Tissue-Derived Mesenchymal Stem Cells and Its Expression Is Controlled by High Glucose. Stem Cells and Development, 21, 1749-1760.
Kitayama, H., Y. Sugimoto, T. Matsuzaki, Y. Ikawa & M. Noda (1989) A ras-related gene with transformation suppressor activity. Cell, 56, 77-84.
Kumamoto, H. & K. Ooya (2006) Immunohistochemical detection of MTI-MMP, RECK, and EMMPRIN in ameloblastic tumors. Journal of Oral Pathology & Medicine, 35, 345-351.
Lam, J. K., M. Y. Chow, Y. Zhang & S. W. Leung (2015) siRNA Versus miRNA as Therapeutics for Gene Silencing. Mol Ther Nucleic Acids, 4, e252.
Laskowski, M., Jr. & I. Kato (1980) Protein inhibitors of proteinases. Annu Rev Biochem, 49, 593-626.
Lee, R. C., R. L. Feinbaum & V. Ambros (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell, 75, 843-54.
Leite, K. R. M., S. T. Reis, N. Viana, D. R. Morais, C. M. Moura, I. A. Silva, J. Pontes, B. Katz & M. Srougi (2015) Controlling RECK miR21 Promotes Tumor Cell Invasion and Is Related to Biochemical Recurrence in Prostate Cancer. Journal of Cancer, 6, 292-301.
Lewis, B. P., C. B. Burge & D. P. Bartel (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell, 120, 15-20.
Lewis, B. P., I. H. Shih, M. W. Jones-Rhoades, D. P. Bartel & C. B. Burge (2003) Prediction of mammalian microRNA targets. Cell, 115, 787-98.
Li, Y., Y. Zhang & Q. Zheng (2005) Expression of RECK gene and MMP-9 in hilar cholangiocarcinoma and its clinical significance. J Huazhong Univ Sci Technolog Med Sci, 25, 552-4.
Lian, H. F., R. R. Zhang, Q. Niu, J. Wang, K. Li, F. K. Liu, W. P. Mu & C. X. Liu (2016) MiR-486-5p inhibits metastasis by targeting neuropilin-2 in gastric cancer. International Journal of Clinical and Experimental Pathology, 9, 5313-5319.
Lin, C. T. (2009) Relationship between Epstein-Barr virus infection and nasopharyngeal carcinoma pathogenesis. Ai Zheng, 28, 791-804.
Lin, C. T., W. Y. Chan, W. Chen, H. M. Huang, H. C. Wu, M. M. Hsu, S. M. Chuang & C. C. Wang (1993) Characterization of seven newly established nasopharyngeal carcinoma cell lines. Lab Invest, 68, 716-27.
Lin, C. T., A. N. Dee, W. Chen & W. Y. Chan (1994) Association of Epstein-Barr virus, human papilloma virus, and cytomegalovirus with nine nasopharyngeal carcinoma cell lines. Lab Invest, 71, 731-6.
Lin, C. T., C. R. Lin, G. K. Tan, W. Chen, A. N. Dee & W. Y. Chan (1997) The mechanism of Epstein-Barr virus infection in nasopharyngeal carcinoma cells. Am J Pathol, 150, 1745-56.
Lin, C. T., C. I. Wong, W. Y. Chan, K. W. Tzung, J. K. Ho, M. M. Hsu & S. M. Chuang (1990) Establishment and characterization of two nasopharyngeal carcinoma cell lines. Lab Invest, 62, 713-24.
Liu, B., Y. Chen & D. K. Clair (2008) ROS and p53: a versatile partnership. Free Radic Biol Med., 44, 1529-1535.
Liu, D., M. Zhang, W. Xie, G. Lan, H. P. Cheng, D. Gong, C. Huang, Y. C. Lv, F. Yao, Y. L. Tan, L. Li, X. L. Zheng & C. K. Tang (2016) MiR-486 regulates cholesterol efflux by targeting HAT1. Biochem Biophys Res Commun, 472, 418-24.
Liu, L. T., H. C. Chang, L. C. Chiang & W. C. Hung (2003) Histone deacetylase inhibitor up-regulates RECK to inhibit MMP-2 activation and cancer cell invasion. Cancer Research, 63, 3069-3072.
M. P. Curado, B. E., H. R. Shin, H. Storm, J. Ferlay, M. Heanue and P. Boyle. 2007. Cancer Incidence in Five Continents. IARC Scientific Publication.
Ma, H., T. Tian, S. Liang, X. Liu, H. Shen, M. Xia, X. Liu, W. Zhang, L. Wang, S. Chen & L. Yu (2016a) Estrogen receptor-mediated miR-486-5p regulation of OLFM4 expression in ovarian cancer. Oncotarget, 7, 10594-605.
Ma, X., J. Wei, L. Zhang, D. Deng, L. Liu, X. Mei, X. He & J. Tian (2016b) miR-486-5p inhibits cell growth of papillary thyroid carcinoma by targeting fibrillin-1. Biomed Pharmacother, 80, 220-6.
Mack, G. S. (2007) MicroRNA gets down to business. Nat Biotechnol, 25, 631-8.
Masui, T., R. Doi, T. Koshiba, K. Fujimoto, S. Tsuji, S. Nakajima, M. Koizumi, E. Toyoda, S. Tulachan, D. Ito, K. Kami, T. Mori, M. Wada, M. Noda & M. Imamura (2003) RECK expression in pancreatic cancer: its correlation with lower invasiveness and better prognosis. Clin Cancer Res, 9, 1779-84.
Mees, S. T., W. A. Mardin, S. Sielker, E. Willscher, N. Senninger, C. Schleicher, M. Colombo-Benkmann & J. Haier (2009) Involvement of CD40 targeting miR-224 and miR-486 on the progression of pancreatic ductal adenocarcinomas. Ann Surg Oncol, 16, 2339-50.
Niculescu, L. S., N. Simionescu, G. M. Sanda, M. G. Carnuta, C. S. Stancu, A. C. Popescu, M. R. Popescu, A. Vlad, D. R. Dimulescu, M. Simionescu & A. V. Sima (2015) MiR-486 and miR-92a Identified in Circulating HDL Discriminate between Stable and Vulnerable Coronary Artery Disease Patients. Plos One, 10.
Nitto, T., T. Inoue & K. Node (2008) Alternative spliced variants in the pantetheinase family of genes expressed in human neutrophils. Gene, 426, 57-64.
Noda, M., J. Oh, R. Takahashi, S. Kondo, H. Kitayama & C. Takahashi (2003) RECK: A novel suppressor of malignancy linking oncogenic signaling to extracellular matrix remodeling. Cancer and Metastasis Reviews, 22, 167-175.
Oh, H. K., A. L. K. Tan, K. Das, C. H. Ooi, N. T. Deng, I. B. Tan, E. Beillard, J. Lee, K. Ramnarayanan, S. Y. Rha, N. Palanisamy, P. M. Voorhoeve & P. Tan (2011) Genomic Loss of miR-486 Regulates Tumor Progression and the OLFM4 Antiapoptotic Factor in Gastric Cancer. Clinical Cancer Research, 17, 2657-2667.
Oh, J., R. Takahashi, S. Kondo, A. Mizoguchi, E. Adachi, R. M. Sasahara, S. Nishimura, Y. Imamura, H. Kitayama, D. B. Alexander, C. Ide, T. P. Horan, T. Arakawa, H. Yoshida, S. Nishikawa, Y. Itoh, M. Seiki, S. Itohara, C. Takahashi & M. Noda (2001) The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis. Cell, 107, 789-800.
Pang, W., X. Tian, F. Bai, R. Han, J. Wang, H. Shen, X. Zhang, Y. Liu, X. Yan, F. Jiang & L. Xing (2014) Pim-1 kinase is a target of miR-486-5p and eukaryotic translation initiation factor 4E, and plays a critical role in lung cancer. Mol Cancer, 13, 240.
Park, S., C. Lee, P. Sabharwal, M. Zhang, C. L. Meyers & S. Sockanathan (2013) GDE2 promotes neurogenesis by glycosylphosphatidylinositol-anchor cleavage of RECK. Science, 339, 324-8.
Plaisance-Bonstaff, K. & R. Renne (2011) Viral miRNAs. Methods Mol Biol, 721, 43-66.
Priscilla, N., Kelly, A. D., M. Jerry, Adams, L. Stephen, Nutt & S. Andreas (2007) Tumor growth need not be driven by rare cancer stem cells. Science, 317, 337.
Quintana, E., M. Shackleton, M. S. Sabel, D. R. Fullen, T. M. Johnson & S. J. Morrison (2008) Efficient tumour formation by single human melanoma cells. Nature, 456, 593-598.
Rask, L., E. Balslev, R. Sokilde, E. Hogdall, H. Flyger, J. Eriksen & T. Litman (2014) Differential expression of miR-139, miR-486 and miR-21 in breast cancer patients sub-classified according to lymph node status. Cellular Oncology, 37, 215-227.
Regenmortel, M. v. 2009. Desk Encyclopedia of Human and Medical Virology.
Ren, C., H. Chen, C. Han, D. Fu, L. Zhou, G. Jin, F. Wang, D. Wang, Y. Chen, L. Ma, X. Zheng & D. Han (2016) miR-486-5p expression pattern in esophageal squamous cell carcinoma, gastric cancer and its prognostic value. Oncotarget, 7, 15840-53.
Roberts, A. P., A. P. Lewis & C. L. Jopling (2011) The role of microRNAs in viral infection. Prog Mol Biol Transl Sci, 102, 101-39.
Rollin, J., S. Regina, C. Blechet, S. Iochmann, S. Guyetant, E. Lemarie, R. Reverdiau & Y. Gruel (2005) Comparative expression of RECK, MMP-2, MMP-9 and VEGF genes in non-small cell lung cancer. Lung Cancer, 49, S143-S143.
Ruvkun, G., V. Ambros, A. Coulson, R. Waterston, J. Sulston & H. R. Horvitz (1989) Molecular genetics of the Caenorhabditis elegans heterochronic gene lin-14. Genetics, 121, 501-16.
Santini, J., J. L. Formento, M. Francoual, G. Milano, M. Scheneider, O. Dassonville & F. Demard (1991a) Characterization, quantification, and potential clinical value of the epidermal growth factor receptor in head and neck squamous cell carcinomas. Head Neck., 3, 132-139.
Santini, J., J. L. Formento, M. Francoual, G. Milano, M. Schneider, O. Dassonville & F. Demard (1991b) Characterization, quantification, and potential clinical value of the epidermal growth factor receptor in head and neck squamous cell carcinomas. Head Neck, 13, 132-9.
Schlott, B., J. Wohnert, C. Icke, M. Hartmann, R. Ramachandran, K. H. Guhrs, E. Glusa, J. Flemming, M. Gorlach, F. Grosse & O. Ohlenschlager (2002) Interaction of Kazal-type inhibitor domains with serine proteinases: Biochemical and structural studies. Journal of Molecular Biology, 318, 533-546.
Shao, Y., Y. Q. Shen, Y. L. Li, C. Liang, B. J. Zhang, S. D. Lu, Y. Y. He, P. Wang, Q. L. Sun, Y. X. Jin & Z. L. Ma (2016) Direct repression of the oncogene CDK4 by the tumor suppressor miR-486-5p in non-small cell lung cancer. Oncotarget, 7, 34011-34021.
Simons, M. J., G. B. Wee, N. E. Day, P. J. Morris, K. Shanmugaratnam & G. B. De-The (1974) Immunogenetic aspects of nasopharyngeal carcinoma: I. Differences in HL-A antigen profiles between patients and control groups. Int J Cancer, 13, 122-34.
Song, S. Y., H. J. Son, E. Nam, J. C. Rhee & C. Park (2006) Expression of reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) as a prognostic indicator in gastric cancer. Eur J Cancer, 42, 101-8.
Span, P. N., C. G. J. F. Sweep, P. Manders, L. V. A. M. Beex, D. Leppert & R. L. P. Lindberg (2003) Matrix metalloproteinase inhibitor reversion-inducing cysteine-rich protein with Kazal motifs - A prognostic marker for good clinical outcome in human breast carcinoma. Cancer, 97, 2710-2715.
Stubbs, M. T., R. Morenweiser, J. Sturzebecher, M. Bauer, W. Bode, R. Huber, G. P. Piechottka, G. Matschiner, C. P. Sommerhoff, H. Fritz & E. A. Auerswald (1997) The three-dimensional structure of recombinant leech-derived tryptase inhibitor in complex with trypsin - Implications for the structure of human mast cell tryptase and its inhibition. Journal of Biological Chemistry, 272, 19931-19937.
Sun, H., C. Cui, F. Xiao, H. Wang, J. Xu, X. Shi, Y. Yang, Q. Zhang, X. Zheng, X. Yang, C. Wu & L. Wang (2015) miR-486 regulates metastasis and chemosensitivity in hepatocellular carcinoma by targeting CLDN10 and CITRON. Hepatol Res, 45, 1312-22.
Takahashi, C., Z. Q. Sheng, T. P. Horan, H. Kitayama, M. Maki, K. Hitomi, Y. Kitaura, S. Takai, R. M. Sasahara, A. Horimoto, Y. Ikawa, B. J. Ratzkin, T. Arakawa & M. Noda (1998) Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK. Proceedings of the National Academy of Sciences of the United States of America, 95, 13221-13226.
Takenaka, K., S. Ishikawa, K. Yanagihara, R. Miyahara, S. Hasegawa, Y. Otake, Y. Morioka, C. Takahashi, M. Noda, H. Ito, H. Wada & F. Tanaka (2005) Prognostic significance of reversion-inducing cysteine-rich protein with Kazal motifs expression in resected pathologic stage IIIA N2 non-small-cell lung cancer. Annals of Surgical Oncology, 12, 817-824.
Takenaka, K., F. Tanaka, C. Takahashi, M. Noda & H. Wada (2004) RECK gene expression in correlation with angiogenesis and angiogenesis-related genes expression in resected non-small cell lung cancer. Journal of Clinical Oncology, 22, 857s-857s.
Takeuchi, T., M. Hisanaga, M. Nagao, N. Ikeda, H. Fujii, F. Koyama, T. Mukogawa, H. Matsumoto, S. Kondo, C. Takahashi, M. Noda & Y. Nakajima (2004) The membrane-anchored matrix metalloproteinase (MMP) regulator RECK in combination with MMP-9 serves as an informative prognostic indicator for colorectal cancer. Clinical Cancer Research, 10, 5572-5579.
Tanzer, A. & P. F. Stadler (2004) Molecular evolution of a microRNA cluster. J Mol Biol, 339, 327-35.
Thomas Maar, J. M. A. S., Herminia Pasantes-Morales (1995) Taurine deficiency in dissociated mouse cerebellar cultures affects neuronal migration. Int. J. Devl Neuroscience, 13, 491-502.
Thompson, L. D. (2007) Update on nasopharyngeal carcinoma. Head Neck Pathol, 1, 81-6.
Tian, F., Y. Shen, Z. Chen, R. Li, J. Lu & Q. Ge (2016) Aberrant miR-181b-5p and miR-486-5p expression in serum and tissue of non-small cell lung cancer. Gene, 591, 338-43.
Tsao, S. W., Y. L. Yip, C. M. Tsang, P. S. Pang, V. M. Lau, G. Zhang & K. W. Lo (2014) Etiological factors of nasopharyngeal carcinoma. Oral Oncol, 50, 330-8.
van der Jagt, M. F. P., F. C. G. J. Sweep, E. T. Waas, T. Hendriks, T. J. M. Ruers, A. H. H. Merry, T. Wobbes & P. N. Span (2006) Correlation of reversion-inducing cysteine-rich protein with kazal motifs (RECK) and extracellular matrix metalloproteinase inducer (EMMPRIN), with MMP-2, MMP-9, and survival in colorectal cancer. Cancer Letters, 237, 289-297.
Van Lent, P. L., P. N. Span, T. R. D. J. Radstake, T. van Lieshout, F. G. J. Sweep & W. B. van den Berg (2004) Decreased expression of the novel metalloproteinase inhibitor RECK (Reversion inducing cysteine-rich protein with kazal motifs) in inflamed synovia of rheumatoid arthritis patients. Arthritis and Rheumatism, 50, S151-S151.
Vandelocht, A., D. Lamba, M. Bauer, R. Huber, T. Friedrich, B. Kroger, W. Hoffken & W. Bode (1995) 2 Heads Are Better Than One - Crystal-Structure of the Insect Derived Double Domain Kazal Inhibitor Rhodniin in Complex with Thrombin. Embo Journal, 14, 5149-5157.
Wang, H. Y., Y. L. Chang, K. F. To, J. S. Hwang, H. Q. Mai, Y. F. Feng, E. T. Chang, C. P. Wang, M. K. Kam, S. L. Cheah, M. Lee, L. Gao, H. Z. Zhang, J. H. He, H. Jiang, P. Q. Ma, X. D. Zhu, L. Zeng, C. Y. Chen, G. Chen, M. Y. Huang, S. Fu, Q. Shao, A. J. Han, H. G. Li, C. K. Shao, P. Y. Huang, C. N. Qian, T. X. Lu, J. T. Li, W. Ye, I. Ernberg, H. K. Ng, J. T. Wee, Y. X. Zeng, H. O. Adami, A. T. Chan & J. Y. Shao (2016) A new prognostic histopathologic classification of nasopharyngeal carcinoma. Chin J Cancer, 35, 41.
Wang, J., X. Tian, R. Han, X. Zhang, X. Wang, H. Shen, L. Xue, Y. Liu, X. Yan, J. Shen, K. Mannoor, J. Deepak, J. M. Donahue, S. A. Stass, L. Xing & F. Jiang (2013) Downregulation of miR-486-5p contributes to tumor progression and metastasis by targeting protumorigenic ARHGAP5 in lung cancer. Oncogene.
Wang, L. S., L. Li, L. Li, S. Chu, K. D. Shiang, M. Li, H. Y. Sun, J. Xu, F. J. Xiao, G. Sun, J. J. Rossi, Y. Ho & R. Bhatia (2015) MicroRNA-486 regulates normal erythropoiesis and enhances growth and modulates drug response in CML progenitors. Blood, 125, 1302-13.
Weimann, B. I. & D. Hermann (1999) Studies on wound healing: effects of calcium D-pantothenate on the migration, proliferation and protein synthesis of human dermal fibroblasts in culture. Int J Vitam Nutr Res., 69, 113-119.
Wilson, R. C. & J. A. Doudna (2013) Molecular Mechanisms of RNA Interference. Annual Review of Biophysics, Vol 42, 42, 217-239.
Xiao, J., Q. Xiang, Y. C. Xiao, Z. J. Su, Z. F. Huang, Q. H. Zhang, Y. Tan, X. K. Li & Y. D. Huang (2010) The effect of transforming growth factor-beta1 on nasopharyngeal carcinoma cells: insensitive to cell growth but functional to TGF-beta/Smad pathway. J Exp Clin Cancer Res, 29, 35.
Xie, X., H. Wang, H. Jin, S. Ouyang, J. Zhou, J. Hu, X. Xi, J. Luo, Y. Zhang & B. Hu (2013) Expression of pAkt affects p53 codon 72 polymorphism-based prediction of response to radiotherapy in nasopharyngeal carcinoma. Radiat Oncol, 8, 117.
Ye, H., X. Yu, J. Xia, X. Tang, L. Tang & F. Chen (2016) MiR-486-3p targeting ECM1 represses cell proliferation and metastasis in cervical cancer. Biomed Pharmacother, 80, 109-14.
Young, L. S. & C. W. Dawson (2014) Epstein-Barr virus and nasopharyngeal carcinoma. Chin J Cancer, 33, 581-90.
Yu, M. C., J. H. C. Ho, S. H. Lai & B. E. Henderson (1986) Cantonese-Style Salted Fish as a Cause of Nasopharyngeal Carcinoma - Report of a Case-Control Study in Hong-Kong. Cancer Research, 46, 956-961.
Yu, W. M. & S. S. Hussain (2009) Incidence of nasopharyngeal carcinoma in Chinese immigrants, compared with Chinese in China and South East Asia: review. J Laryngol Otol, 123, 1067-74.
Zhang, R., C. Lan, H. Pei, G. Duan, L. Huang & L. Li (2015) Expression of circulating miR-486 and miR-150 in patients with acute myocardial infarction. BMC Cardiovasc Disord, 15, 51.
Zhu, J., Y. Zeng, C. Xu, H. Qin, Z. Lei, D. Shen, Z. Liu & J. A. Huang (2015) Expression profile analysis of microRNAs and downregulated miR-486-5p and miR-30a-5p in non-small cell lung cancer. Oncol Rep, 34, 1779-86.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關論文
 
無相關期刊
 
無相關點閱論文
 
系統版面圖檔 系統版面圖檔