S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Medicine (의학과) Theses (Ph.D. / Sc.D._의학과)
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.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.
List of tables and figures v
List of abbreviations vii
Material and methods 7
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.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.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||-|
- Appears in Collections:
- College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Theses (Ph.D. / Sc.D._의학과)