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NFE2L1의 미토콘드리아 손상 반응성과 간암세포주의 침윤활성 조절 연구
- Alternative Title
- Gyeong-Hyeon Kim
- Author(s)
- 김경현
- Alternative Author(s)
- Gyeong-Hyeon Kim
- Advisor
- 윤계순
- Department
- 일반대학원 의생명과학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2017-02
- Language
- eng
- Keyword
- mitochondria; invasiveness
- Alternative Abstract
- Mitochondrial dysfunction is an important metabolic feature in human cancer. However, underlying mechanisms how mitochondrial dysfunction affects tumorigenesis remain unclear. The current study focused on the role of NFE2L1 transcription factor which was previously identified as a mitochondrial defect-responsive gene in hepatoma cell invasiveness. NFE2L1 expression is increased in SNU354 and SNU423 hepatoma cells which have mitochondrial defects and high invasion activity. Knockdown of NFE2L1 decreased hepatoma cell invasion activity in SNU354 and SNU423 cells, implying that NFE2L1 is a key regulator of invasion activity. Next, we investigated how NFE2L1 expression is regulated by mitochondrial dysfunction. SNU354 and SNU423 cells showed high cytosolic Ca2+ and reactive oxygen species (ROS) levels and both increased cytosolic Ca2+ and ROS levels were involved in NFE2L1 expression. Analysis of transcription factor binding sites within -2800 to +200 NFE2L1 promoter region using TRANSFAC program identified 11 potential transcription factors to regulate NFE2L1 transcription. Among them, sterol regulatory element-binding protein 1 (SREBP1) was found to regulate NFE2L1 expression in SNU354 cell. In conclusion, our results suggest that NFE2L1 is one of key transcription regulators to control hepatoma cell invasiveness and its transcription is regulated by mitochondria driven Ca2+ or ROS signaling. Also, SREBP1 may be an upstream transcription factor of the NFE2L1 transcription. These findings emphasize the involvement of NFE2L1 in hepatocellular carcinoma (HCC), providing its potential role as a therapeutic target of HCC, and expand our knowledge of mitochondrial defect-mediated mitochondrial retrograde signaling in tumorigenesis.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Biomedical Sciences > 3. Theses(Master)
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