RNA 결합 단백질 PTBP1에 의한 간세포암의 성장 조절.
Polypyrimidine Tract-binding protein promotes hepatocellular growth via regulating cyclin D and CDK expression.
- 주제(키워드) 간암 , PTBP1
- 발행기관 아주대학교
- 지도교수 김욱
- 발행년도 2016
- 학위수여년월 2016. 2
- 학위명 석사
- 학과 및 전공 일반대학원 분자과학기술학과
- 실제URI http://www.dcollection.net/handler/ajou/000000022034
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Polypyrimidine tract-binding protein (PTBP1, also named hnRNP I) is a RNA-binding protein which has multiple functions related to the wide range of RNA metabolisms. Although several reports have shown that PTBP1 expression level is altered in various cancer types, the role of PTBP1 in hepatocellular carcinoma (HCC) is unknown. Here, I report that PTBP1 is substantially upregulated in human HCC and the patients highly expressing PTBP1 survived shorter than one with lower expression. Consistently, silencing PTBP1 by siRNA in HCC cell-line Hep3B cells induced growth arrest at G1 phase, suppressed colony forming ability of Hep3B, and decreased levels of pivotal cell cycle regulators including cyclin D1 and D3 and cyclin-dependent kinase 6 (cdk6). Ribonucleoprotein immunoprecipitation analyses showed that PTBP1 associated with their mRNAs. Furthermore, PTBP1 expression in Hep3B cells was downregulated by miR-194, whose expression was reduced in human HCC patients. Taken together, these findings suggest that PTBP1 contributes to liver cancer progression. Thus, modulation of PTBP1 might be a novel therapeutic strategy against liver cancer.
more목차
Ⅰ. INTRODUCTION 1
Ⅱ. MATERIALS and METHODS 4
1. Cell culture, transfection, small interfering RNA 4
2. Western blot analysis 4
3. DNA content analysis 4
4. MTS assay 5
5. Colony forming assay 5
6. Ribonucleoprotein-complex Immunoprecipitation 6
7. RT-qPCR 7
8. Statistical analysis 7
Ⅲ. RESULTS 9
1. PTBP1 is up-regulated in human HCC tissues and associated with overall survival 9
2. Knockdown of PTBP1 inhibits G1/S transition and cell proliferation of Hep3B cells 16
3. PTBP1 regulates the expression of cyclin D1, cyclin D3 and Cdk6 21
4. MicroRNA-194 is a novel regulator of PTBP1 expression 28
Ⅳ. DISCUSSION 33
Ⅴ. REFERENCE 36
Ⅵ. ABSTRACT IN KOREAN(국문초록) 41
