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microRNA-192 suppresses leptomeningeal dissemination of medullpblastoma by modulating cell proliferation and anchoring through the regulation dihydrofolate reductase, integrin subunits, and CD 47 : 수모세포종 전이와 관련된 microRNA-192의 역할
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 정희원 | - |
dc.contributor.author | 양승엽 | - |
dc.date.accessioned | 2017-07-14T01:31:17Z | - |
dc.date.available | 2017-07-14T01:31:17Z | - |
dc.date.issued | 2015-02 | - |
dc.identifier.other | 000000025590 | - |
dc.identifier.uri | https://hdl.handle.net/10371/122053 | - |
dc.description | 학위논문 (박사)-- 서울대학교 대학원 : 의학과, 2015. 2. 정희원. | - |
dc.description.abstract | Introduction: The main cause of death in medulloblastoma is recurrence associated with leptomeningeal dissemination. Although the molecular basis of medulloblastoma has received considerable attention over the past decade, the role of microRNAs (miRNAs) in the acquisition of metastatic phenotype remains poorly understood. This study aimed to identify the miRNA involved in leptomeningeal dissemination and to elucidate its target mechanisms.
Materials and methods: We analyzed the miRNA expression profiles of 29 medulloblastomas according to the presence of cerebrospinal fluid (CSF) seeding. Differentially expressed miRNAs (DEmiRNAs) were validated on 29 medulloblastoma tissues and three medulloblastoma cells. The biological function of the selected miRNA was evaluated using in vitro studies. Results: A total of 12 DEmiRNAs were identified including miRNA-192 in medulloblastoma with seeding. The reduced expression of miRNA-192 was confirmed in the tumor seeding group and in the medulloblastoma cell lines. Overexpression of miRNA-192 inhibited cellular proliferation targeting dihydrofolate reductase (DHFR). miRNA-192 decreased cellular anchoring via the repression of integrin subunits (αV, β1, and β3) and CD47. Conclusions: Medulloblastoma with seeding showed specific DEmiRNAs compared to those without. microRNA-192 suppresses leptomeningeal dissemination of medulloblastoma by modulating cell proliferation and anchoring ability. | - |
dc.description.tableofcontents | Abstract i
Contents iv List of tables and figures v List of abbreviations vii Introduction 3 Material and methods 7 Results 26 Discussion 41 References 55 Abstract in Korean 98 LIST OF TABLES Table 1. Characteristics of the patients with medulloblastoma (N=29) 63 Table 2. Differentially expressed miRNAs in tumor seeding group compared to tumor non-seeding group 65 LIST OF FIGURES Figure 1. miRNA-192 in medulloblastoma tissues and cells 67 Figure 2. Functional study of miRNA-192 transfection in medulloblastoma cells 71 Figure 3. DHFR is a direct target of miRNA-192 76 Figure 4. miRNA-192 in invasion and EMT of medulloblastoma 81 Figure 5. Cell adhesion assay 86 Figure 6. miRNA-192 inhibits expression of specific α and β integrin subunits as well as CD47 in vitro 88 | - |
dc.format | application/pdf | - |
dc.format.extent | 2035290 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | Medulloblastoma | - |
dc.subject | microRNA-192 | - |
dc.subject | Integrins | - |
dc.subject | CD47 | - |
dc.subject | Dihydrofolate reductase | - |
dc.subject | Seeding | - |
dc.subject.ddc | 610 | - |
dc.title | microRNA-192 suppresses leptomeningeal dissemination of medullpblastoma by modulating cell proliferation and anchoring through the regulation dihydrofolate reductase, integrin subunits, and CD 47 | - |
dc.title.alternative | 수모세포종 전이와 관련된 microRNA-192의 역할 | - |
dc.type | Thesis | - |
dc.contributor.AlternativeAuthor | microRNA-192 suppresses leptomeningeal dissemination of medulloblastoma by modulating cell proliferation and anchoring through the regulation of dihydrofolate reductase, integrin subunits, and CD 47 | - |
dc.description.degree | Doctor | - |
dc.citation.pages | viii, 99 | - |
dc.contributor.affiliation | 의과대학 의학과 | - |
dc.date.awarded | 2015-02 | - |
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