Low-dose irradiation promotes Rad51 expression by down-regulating miR-193b-3p in hepatocytes

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作者
Eon-Seok Lee
Yeo Jin Won
Byoung-Chul Kim
Daeui Park
Jin-Han Bae
Seong-Joon Park
Sung Jin Noh
Yeong-Rok Kang
Si Ho Choi
Je-Hyun Yoon
Kyu Heo
Kwangmo Yang
Tae Gen Son
机构
[1] Research Center,Department of Radiation Oncology
[2] Dongnam Institute of Radiological and Medical Science,Department of Biochemistry and Molecular Biology
[3] Korea Institute of Radiological and Medical Sciences,undefined
[4] In silico Toxicology Research Center,undefined
[5] Korea Insititute of Toxciology,undefined
[6] Medical University of South Carolina,undefined
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摘要
Current evidence indicates that there is a relationship between microRNA (miRNA)-mediated gene silencing and low-dose irradiation (LDIR) responses. Here, alterations of miRNA expression in response to LDIR exposure in male BALB/c mice and three different types of hepatocytes were investigated. The miRNome of the LDIR-exposed mouse spleens (0.01 Gy, 6.5 mGy/h) was analyzed, and the expression of miRNA and mRNA was validated by qRT-PCR. Western blotting, chromatin immunoprecipitation (ChIP), and luciferase assays were also performed to evaluate the interaction between miRNAs and their target genes and to gain insight into the regulation of miRNA expression. The expression of miRNA-193b-3p was down-regulated in the mouse spleen and liver and in various hepatocytes (NCTC, Hepa, and HepG2 cell lines) in response to LDIR. The down-regulation of miR-193b-3p expression was caused by histone deacetylation on the miR-193b-3p promoter in the HepG2 cells irradiated with 0.01 Gy. However, the alteration of histone deacetylation and miR-193b-3p and Rad51 expression in response to LDIR was restored by pretreatment with N-acetyl-cyctein. In conclusion, we provide evidence that miRNA responses to LDIR include the modulation of cellular stress responses and repair mechanisms.
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