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MDM2-p53 mediate a miR-181c-3p/LIF axis to regulate low dose-rate radiation-induced DNA damage in human B lymphocytes.
Chen, Yonglin; Gong, Yaqi; Qin, Hui; Wei, Shuang; Wei, Yuanyun; Yu, Yueqiu; Lin, Xiang; Shuai, Peimeng; Wang, Tiantian; Guo, Caimao; Wang, Qingyu; Li, Guoqing; Meng, Lijuan; Yi, Lan.
Afiliação
  • Chen Y; Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • Gong Y; Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • Qin H; Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • Wei S; Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • Wei Y; Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • Yu Y; Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • Lin X; Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • Shuai P; Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • Wang T; Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • Guo C; Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • Wang Q; Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • Li G; Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • Meng L; The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China. Electronic address: lijuanmeng@usc.edu.cn.
  • Yi L; Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China. Electronic address: yilanoky@126.com.
Ecotoxicol Environ Saf ; 270: 115848, 2024 Jan 15.
Article em En | MEDLINE | ID: mdl-38134636
ABSTRACT

PURPOSE:

Prolonged exposure to low dose-rate radiation (LDRR) is of growing concern to public health. Recent evidences indicates that LDRR causes deleterious health effects and is closely related to miRNAs. The aim of our study is to investigate the relationship between miRNAs and DNA damage caused by LDRR. MATERIALS AND

METHODS:

In this study, we irradiated C57BL/6J mice with 12.5µGy/h dose of γ ray emitted from uranium ore for 8 h a day for 120 days at a total dose of 12 mGy, and identified differentially expressed miRNAs from the mice long-term exposed to LDRR through isolating serum RNAs, constructing small RNA library, Illumina sequencing. To further investigate the role of differential miRNA under LDRR，we first built DNA damage model in Immortal B cells irradiated with 12.5µGy/h dose of γ ray for 28 days at a total dose of 9.4 mGy. Then, we chose the highly conserved miR-181c-3p among 12 miRNA and its mechanism in alleviating DNA damage induced by LDRR was studied by transfection, quantitative PCR, luciferase assay, and Western blot. RESULTS AND

CONCLUSIONS:

We have found that 12 differentially expressed miRNAs including miR-181c-3p in serum isolated from irradiated mice. Analysis of GO and KEGG indicated that target genes of theses 12 miRNA enriched in pathways related to membrane, protein binding and cancer. Long-term exposure to LDRR induced upregulation of gamma-H2A histone family member X (γ-H2AX) expression, a classical biomarker for DNA damage in B cells. miR-181c-3p inhibited Leukemia inhibitory factor (LIF) expression via combining its 3'UTR. LIF, MDM2, p53, and p-p53-s6 were upregulated after exposure to LDRR. In irradiated B cells, Transfection of miR-181c-3p reduced γ-H2AX expression and suppressed LIF and MDM2 protein levels, whereas p-p53-s6 expression was increased. As expected, the effect of LIF inhibition on irradiated B cells was similar to miR-181c-3p overexpression. Our results suggest that LDRR alters miRNA expression and induces DNA damage. Furthermore, miR-181c-3p can alleviate LDRR-induced DNA damage via the LIF/MDM2/p-p53-s6 pathway in human B lymphocytes. This could provide the basis for prevention and treatment of LDRR injury.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteína Supressora de Tumor p53 / MicroRNAs Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteína Supressora de Tumor p53 / MicroRNAs Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article