ABSTRACT
The role of the pprI gene from Deinococcus radiodurans R1 in therapy of acute radiation injury of a mammalian host was investigated. We injected a plasmid containing the pprI gene into the muscle of mice exposed to total 6Gy of 60Co γ-ray radiation. After injection, we used in vivo gene electroporation technology to transfer the pprI gene into the cell. We found the PprI protein was expressed significantly at 1 d after irradiation, but there was no expression of pprI gene 7 d post-irradiation. The expression of pprI gene evidently decreased the death rate of mice exposed to lethal dose radiation, significantly relieved effects on blood cells in the acute stage, shortened the persistence time of the decrease of lymphocytes, and decreased the apoptotic rates of spleen cells, thymocytes and bone marrow cells. The expression of Rad51 protein in the lungs, livers, and kidneys was significantly higher in the mice treated with the pprI plasmid after irradiation. However, there were no obvious differences for Rad52 protein expression. We conclude that the prokaryotic pprI gene of D. radiodurans R1 first was expressed in mammalian cells. The expressed prokaryotic PprI protein has distinct effects of the prevention and treatment on acute radiation injury of mammal. The effects of radio-resistance may relate to expression of Rad51 protein which is homologous with RecA from D. radiodurans.
Subject(s)
Bacterial Proteins/genetics , DNA Repair/genetics , Deinococcus/genetics , Genes, Bacterial , Radiation Injuries/genetics , Radiation Tolerance/genetics , Acute Disease , Animals , DNA Damage/genetics , Dose-Response Relationship, Radiation , Gamma Rays , Male , Mice , Mice, Inbred BALB C , Mice, Transgenic , Radiation Injuries/mortality , Radiation Injuries/prevention & controlABSTRACT
BACKGROUND: Renal cell carcinoma (RCC) is a malignancy with a poor prognosis. We aimed to explore whether the expression of Long Non-Coding RNA (LncRNA) growth arrest-specific transcript 5 (GAS5) is associated with RCC genesis. METHODS: We selected twelve clinical samples diagnosed for renal clear cell carcinoma and found that the LncRNA GAS5 transcript levels were significantly reduced relative to those in adjacent unaffected normal renal tissues. RESULTS: In addition, expression of GAS5 was lower in the RCC cell line A498 than that in normal renal cell line HK-2. Furthermore, using functional expression cloning, we found that overexpression of GAS5 in A498 cells inhibited cell proliferation, induced cell apoptosis and arrested cell cycling. At the same time, the migration and invasion potential of A498 cells were inhibited compared to control groups. CONCLUSION: Our study provided the first evidence that a decrease in GAS5 expression is associated with RCC genesis and progression and overexpression of GAS5 can act as a tumor suppressor for RCC, providing a potential attractive therapeutic approach for this malignancy.
