RNA 결합 단백질 HuD에 의한 췌장 베타세포 성장 조절
RNA-binding protein HuD inhibits pancreatic beta-cell proliferation by regulating p27 expression
- 주제(키워드) pancreatic beta-cell , RNA-binding protein
- 발행기관 아주대학교
- 지도교수 김욱
- 발행년도 2015
- 학위수여년월 2015. 2
- 학위명 석사
- 학과 및 전공 일반대학원 분자과학기술학과
- 실제URI http://www.dcollection.net/handler/ajou/000000019504
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
RNA-binding protein HuD is present in pancreatic β cells, where it controls insulin mRNA translation and insulin production. However, direct regulation of β-cell proliferation by HuD has not been studied. Here, I show that HuD negatively regulates β-cell proliferation by increasing p27 level. HuD silencing decreased p27 level, leading to increased β-cell proliferation. Conversely, HuD overexpression induced G1 arrest by enhancing p27 expression. HuD silencing also decreased p27 level, resulting in enhanced β-cell proliferation, in immortalized β cells lacking insulin receptor, suggesting that HuD regulates p27 level in insulin independent manner. Together with the discovery that intratumoral injection of HuD siRNA with the carriers promoted insulinoma growth by reducing p27 level, these results identify HuD as a pivotal regulator of pancreatic β-cell proliferation.
more목차
Ⅰ. INTRODUCTION
Ⅱ. MATERIALS and METHODS
1. Cell culture, transfection, small interfering RNA, plasmids, and treatments
2. Western blot analysis
3. DNA content analysis
4. Immunofluorescence staining and image analysis
5. Animal maintenance and tumor xenograft experiments
6. Treatment of tumors with functional siRNAs
7. Statistical analysis
Ⅲ. RESULTS
1. Silencing HuD decreases p27 expression in pancreatic β-cell lines
2. Overexpression of HuD prevents cell cycle progression in pancreatic β cells
3. Analysis of p27 level and cell cycle progression in βTC6 cell lines that were stably transfected with shHuD
4. Effect of HuD on p27 level and cell cycle progression in the insulin receptor-deficient β-cell lines
5. Intratumoral injection of HuD siRNA enhances insulinoma progression in mouse xenograft model
Ⅳ. DISCUSSION
Ⅴ. REFERENCE
Ⅵ. ABSTRACT IN KOREAN(국문초록)
