2022 Fiscal Year Research-status Report
The role of mitophagy in radioresistance of cancers
| Project/Area Number |
22K20795
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| Research Institution | Nagasaki University |
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Principal Investigator |
YAN Chen 長崎大学, 原爆後障害医療研究所, 講師 (70968396)
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| Project Period (FY) |
2022-08-31 – 2024-03-31
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| Keywords | Radioresistance / Mitophagy / Cancer |
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| Outline of Annual Research Achievements |
Human cancer cells (HCT8, A549, MCF7 and MDA-MB-453) were used in this study. The expression of DNA damage marker (γH2AX), cyclin-dependent kinase inhibitor (p21), and the level of mitochondrial superoxide were significantly increased in human cancer cells 8, 24, and 48 hours after 5 Gy X-rays exposure.
Interestingly, radiation exposure significantly increased the expression of several mitophagy receptors 48 hours after 5 Gy X-rays exposure, but not 8 or 24 hours after 5 Gy X-rays exposure. It suggests that radiation exposure induces mitophagy activity. To verify the role of mitophagy in regulating the radioresistance of cancer cells, we used small interfering RNA to knockdown the expression of radiation-induced mitophagy receptors. Western blot analysis showed that the knockdown of some radiation-induced mitophagy receptors enhanced the expression of γH2AX and the level of mitochondrial superoxide in cancer cells 48 hours after 5 Gy X-rays exposure. We are still investigating how the overexpression of the key mitophagy receptors will affect the radioresistance of cancer cells.
Our data suggests that mitophagy may regulate the acquired radioresistance of cancers following radiotherapy.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Our data shown that radiation exposure induces mitophagy activity. Moreover, knockdown of radiation-induced mitophagy receptors enhances the radiosensitivity of cancer cells.
We are now investigating how the overexpression of the key mitophagy receptors will affect the radioresistance of cancer cells. Furthermore, it needs to be clarified about the detailed mechanism of mitophagy in regulating radioresistance of cancers and help us to develop a novel therapeutic strategy/approach for cancers.
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| Strategy for Future Research Activity |
Further interventional experiments are asked to reveal the precise role and the detailed mechanism of mitophagy in regulating the radioresistance of cancers in vitro and in vivo.
1. To verify the detailed mechanism of mitophagy in regulating the radioresistance of cancer cells in vivo, we will investigate how the overexpression or knockdown of the key mitophagy receptors will affect the key molecules of redox signaling, cell cycle pathway and DNA damage signaling in cancer cells by PCR array analysis.
2. To verify the role of mitophagy in regulating the radioresistance of cancer cells in vivo, BALB/c-nu/nu mice will be injected subcutaneously with cancer cells stable overexpression or knockdown the key mitophagy-associated molecules. Mice will be treated with radiotherapy. Tumor volumes and weights will be measured.
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| Causes of Carryover |
As some existing reagents and antibodies in our department were used in this study, it resulted in an incurring amount to be used next fiscal year.
The incurring amount will be used for the cost of PCR array analysis and in vivo experiments to be carried out in the next fiscal year.
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