Study on the Effect of SIRT3 Expression on Mitochondrial DNA Copy Number in Human Cancer Cell Lines
| Autor: | Yao-Wen Liu, 劉耀文 |
|---|---|
| Rok vydání: | 2013 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 101 The mutations in mitochondrial DNA (mtDNA) have been found in many human cancers. The phenomena could lead cancer cells to change their way of energy metabolism, increase the production of reactive oxygen species (ROS) and reduce their sensitivity to drugs. However, the mechanism for maintaining mitochondrial genetic stability and mtDNA copy number is still unknown. Sirtuins (SIRT1–7) are the mammalian homologues of the Sir2 gene in Saccharomyces cerevisiae. Besides, SIRT3 plays an important role in regulation of maintaining mitochondrial integrity and function. Previous studies found that SIRT3 can interact with p53, which can abolish the p53 signaling in apoptosis, growth arrest and aging. The other studies also showed that there is reduced mtDNA copy number in SIRT3 knockout mice with aging. Thus, the aim of this study is to investigate the effect of SIRT3 expression on mtDNA copy number in human cancer cell lines. The results showed that SIRT3 can be overexpressed via pcDNA™3.1 / myc-His vector and the transfected SIRT3 is functional. In addition, I also used the SIRT3 based on pcDNA vector to investigate mtDNA copy number. The results showed that mtDNA copy number was not up-regulated. Then I used SIRT3 shRNA based on pLKO.1 vector to knockdown SIRT3. The results showed that it can actually reduce the expression of SIRT3 in cancer cells. However, mtDNA copy number was not down-regulated in most of these cells except for HeLa cells. Based on these findings, SIRT3 can regulate mtDNA copy number in HeLa cells, but the mechanism needs to be further studied. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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