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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 阮雪芬 | - |
| dc.contributor.author | Chien-Wei Tseng | en |
| dc.contributor.author | 曾建偉 | zh_TW |
| dc.date.accessioned | 2021-05-20T21:01:17Z | - |
| dc.date.available | 2014-07-27 | - |
| dc.date.available | 2021-05-20T21:01:17Z | - |
| dc.date.copyright | 2011-07-27 | - |
| dc.date.issued | 2011 | - |
| dc.date.submitted | 2011-07-20 | - |
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M., Gu, Q., et al., Serum macrophage migration-inhibitory factor as a diagnostic and prognostic biomarker for gastric cancer. Cancer 2009, 115, 5441-5449. [82] Lim, J. W., Kim, H., Kim, J. M., Kim, J. S., et al., Cellular stress-related protein expression in Helicobacter pylori-infected gastric epithelial AGS cells. Int J Biochem Cell Biol 2004, 36, 1624-1634. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/10091 | - |
| dc.description.abstract | 胃癌在全世界中為癌症致死率的第二名(世界衛生組織2009年報導)。
被診斷晚末期的胃癌病人五年存活率不到35%。較差的預後能力主要與腫瘤轉移有關。此外，有些微型核醣核酸被報導與腫瘤相關，其功能可能是致癌基因或腫瘤抑制基因，並且涉及了腫瘤形成及癌症發展。在本研究中，我們研究胃癌轉移的機制並鑑定出一個抗轉移的微型核醣核酸-148a，它在腫瘤組織中的表現較低。Kaplan–Meier存活方法顯示，相較於含有較低微型核醣核酸-148a含量的病人(32.1%)，其含有較高微型核醣核酸-148a含量的病人具有較高的五年整體存活率 (71.4%) (P = 0.03)。臨床資料指出微型核醣核酸-148a表現量增加與腫瘤遠處轉移(P = 0.043)、器官侵犯 (P = 0.013) 及腹膜侵犯 (P = 0.04) 有高度相關性。大量表現微型核醣核酸-148a減少腫瘤細胞侵犯、轉移及附著能力。此外，大量表現微型核醣核酸-148a抑制細胞生長並誘導細胞凋亡。我們利用了同位素標記相對和絕對定量方法分析微型核醣核酸-148a所調控的蛋白質體表現。微型核醣核酸-148a所調控的蛋白質體與腫瘤發展有高度相關性，其包括了細胞移動、生長與增生以及細胞凋亡。這些結果與我們之前的結果一致，微型核醣核酸-148a抑制胃癌細胞轉移相關的功能。另一方面，進一步的利用了冷光酶分析方法，我們確認了微型核醣核酸-148a可以直接調控14-3-3β表現。14-3-3β在腫瘤組織中的表現增加 (N = 40, P < 0.01)，而且血液14-3-3β在胃癌病人的含量也顯著的比正常人高(N = 63) (P < 0.0001)。具有較高血液14-3-3β含量的病人有較差的整體存活率(P = 0.038)。大量表現14-3-3β增加了腫瘤細胞生長、侵犯與移動能力。綜合上述結果，14-3-3β涉及了胃癌的轉移。微型核醣核酸-148a也許功能上是個腫瘤抑制基因，並且透過調控一個有潛力作為胃癌偵測與預後的14-3-3β生物標記表現以抑制了腫瘤細胞的轉移。 | zh_TW |
| dc.description.abstract | Gastric cancer is the second leading cause of cancer deaths worldwide (WHO 2009 report). Patients diagnosed with advanced stages have a survival rate of less than 35% beyond 5 years. The poor prognosis is mainly related to tumor metastasis. In addition, some microRNAs (miRNAs) are reported as oncomirs which function as either oncogenes or tumor suppressors and involved in tumorigenesis and cancer progression. Here, we studied the mechanisms of gastric cancer metastasis and identified an antimetastatic miRNA, miR-148a, that was down-regulated in tumor tissues. Kaplan–Meier survival method revealed that patients with higher miR-148a expression levels had higher 5-year overall survival rates (71.4%) compared with patients with low miR-148a levels (32.1%, P = 0.03). Clinical data indicated that elevated miR-148a levels highly correlated with distant metastasis (P = 0.043), organ (P = 0.013) and peritoneal invasion (P = 0.04). Over-expression of miR-148a could decrease invasiveness, migration and adhesion of tumor cells. Moreover, Over-expression of miR-148a could repress cell growth and induce cell apoptosis. We further used isobaric tag for relative and absolute quantitation (iTRAQ) method to analyze miR-148a-regulated proteome. The results showed that miR-148a-regulated proteome was closely related with tumor progression, including cell movement, growth and proliferation as well as cell death. These results are consistent with our previous data that miR-148a suppresses metastasis-related functions of gastric cancer cells. On the other hand, we verified that miR-148a could directly regulate 14-3-3β expression using luciferase assay. 14-3-3β levels were elevated in tumor tissues (N = 40, P < 0.01), and serum 14-3-3β levels in cancer patients (N = 145) were also significantly higher than healthy controls (N = 63) (P < 0.0001). Patients with higher serum 14-3-3β levels had worse overall survival (P = 0.038). Over-expression of 14-3-3β enhanced the growth, invasiveness and migration of tumor cells. In conclusion, 14-3-3β is involved in metastasis of gastric cancer. miR-148a may function as a tumor suppressor in gastric cancer, suppressing cell metastasis through targeting 14-3-3β, a potential detective and prognostic marker in gastric cancer. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-20T21:01:17Z (GMT). No. of bitstreams: 1
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| dc.description.tableofcontents | 口試委員會審定書 I
Acknowledgments II 中文摘要 IV ABSTRACT V CONTENTS VII LIST OF FINGURES X LIST OF TABLES XII Chapter 1 Introduction 1 1.1 Biogenesis of miRNAs and Their Roles in Cancers 1 1.2 Analysis of Correlation Between miRNAs and Target Genes 1 1.3 miRNA-regulated Network and Biological Functions 2 1.4 miRNA-regulated Proteome and Associated Biological Functions 3 1.5 14-3-3β 4 1.5.1 Role of 14-3-3β in Cancers 4 1.5.2 Biomarkers for Gastric Cancer 5 1.6 Motivation 6 Chapter 2 Materials and Methods 7 2.1 Expression Profiles of miRNAs and mRNA 7 2.2 Tissue Specimens 8 2.3 MiRNA-regulated PIN Identification and Analysis 9 2.4 qRT-PCR for miRNA 10 2.5 Cell Culture and Authentication of Cell Lines 10 2.6 Cell Invasion and Migration Assays Using Boyden Chambers 10 2.7 Wound Healing Assay 11 2.8 Cell Adhesion Assay 11 2. 9 Cell Proliferation Assay 12 2.10 Luciferase Reporter Assay 12 2.11 Protein Extraction 13 2.12 Immunoblotting 14 2.13 Isobaric Tag for Relative and Absolute Quantitation (iTRAQ) 14 2.13.1 Gel-Assisted Digestion of Cell Lysate 15 2.13.2 iTRAQ Labeling and Fractionation by Strong Cation Exchange (SCX) Chromatograph 15 2.13.3 LC-MS/MS Analysis 16 2.13.4 Data Processing and Analysis 17 2.14 Ingenuity Pathway Analysis (IPA) 18 2.15 Gastric Cancer Patients and Clinical Data 19 2.16 Blood and Tissue Sample Collection 20 2.17 ELISA for 14-3-3β 20 2.18 Construction of the 14-3-3β Over-expressing Plasmid 21 2.19 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) Assay for Cell Growth 21 2.20 Two Dimensional Electrophoresis and Image Analysis 21 2.21 In-gel Digestion and Mass Spectrometry 22 2.22 Statistical Analysis 24 Chapter 3 Results 26 3.1 MicroRNA-regulated PINs in Gastric Cancer 26 3.2 The Potential Functions of Oncomir-regulated PINs 28 3.3 MiR-148a-regulated PIN and Its Potential Functions in Gastric Cancer 28 3.4 PAI-1, ITGB8, VAV2 and ITGA5 Are Oncogenes and Direct Targets of MiR-148a 29 3.5 The Correlation Between miR-148a and Clinicopathological Factors 31 3.6 MiR-148a Inhibits Cell Invasion, Migration, Adhesion and Growth 31 3.7 miR-148a Induces Apoptosis of Gastric Cancer Cells 32 3.8 miR-148a-regulated Proteome and Associated Biological Functions 32 3.9 14-3-3β Is a Direct Target of miR-148a 34 3.10 14-3-3β Expression Is Positively Correlated with Aggressive Phenotypes of Gastric Cancer Cells 35 3.11 Over-expression of 14-3-3β Enhances Cancer Cell Invasion, Migration and Growth 37 3.12 14-3-3β Expression in Tumor Tissues and Serum from Gastric Cancer Patients 37 3.13 Serum 14-3-3β Levels and Overall and Recurrence-free Survival 38 3.14 Serum 14-3-3β Levels Decrease after Gastrectomy with D2 Lymphadenectomy 39 3.15 ROC Curves of 14-3-3β in Gastric Cancer 39 3.16 The Relationship Between 14-3-3β Expression Level and Metastatic Lymph Node Number, Tumor Size and Cancer Stage 40 Chapter 4 Discussion 41 Chapter 5 Conclusion 46 Chapter 6 References 48 Appendix 95 | - |
| dc.language.iso | en | - |
| dc.title | MicroRNA-148a與其標靶基因14-3-3β在胃癌轉移機制之探討 | zh_TW |
| dc.title | The Metastatic Mechanism of MicroRNA-148a and Its Target Gene 14-3-3β in Gastric Cancer | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 99-2 | - |
| dc.description.degree | 博士 | - |
| dc.contributor.oralexamcommittee | 陳炯年,黃宣誠,李岳倫,陳倩瑜 | - |
| dc.subject.keyword | 微型核醣核酸-148a,14-3-3β,胃癌,轉移,生物標記, | zh_TW |
| dc.subject.keyword | miR-148a,14-3-3β,gastric cancer,metastasis,biomarker, | en |
| dc.relation.page | 136 | - |
| dc.rights.note | 同意授權(全球公開) | - |
| dc.date.accepted | 2011-07-20 | - |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 分子與細胞生物學研究所 | zh_TW |
| 顯示於系所單位： | 分子與細胞生物學研究所 | |
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