Frontiers in Oncology (Feb 2021)

Analysis of miRNA-mRNA Crosstalk in Radiation-Induced Mouse Thymic Lymphomas to Identify miR-486 as a Critical Regulator by Targeting IGF2BP3 mRNA

  • Hainan Zhao,
  • Hainan Zhao,
  • Suhe Dong,
  • Jicong Du,
  • Penglin Xia,
  • Ruling Liu,
  • Tingting Liu,
  • Yajie Yang,
  • Ying Cheng,
  • Jianming Cai,
  • Cong Liu,
  • Fu Gao,
  • Hu Liu

DOI
https://doi.org/10.3389/fonc.2020.574001
Journal volume & issue
Vol. 10

Abstract

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Ionizing radiation is one of the common environmental carcinogens. miRNAs play critical roles in the processes of tumor occurrence, development, metastasis. However, the relationship between radiation-induced carcinogenesis and miRNA rarely reported. This study is aimed to investigate the effect of miRNAs on radiation-induced carcinogenesis. In this study we established the radiation-induced thymic lymphoma mice model. By using miRNA array of RTL tissue and predicting for miRNAs target genes, a miRNA-mRNA crosstalk network was established. Based on this network, we identified a critical miRNA, miR-486, which was the most down-regulated in the radiation-induced carcinogenesis. Then the function of miR-486 was confirmed by using knockout mice and cellular experiments. As a result, miR-486 could inhibit proliferation of mouse lymphoma cells by targeting IGF2BP3 mRNA. The adenovirus over-expression miR-486 vector reduced tumorigenesis in vivo. MiR-486 knockout mice have a strong tendency of radiation-induced carcinogenesis. In conclusion, miR-486 inhibits the proliferation of lymphoma cells and tumorigenesis induced by radiation through targeting IGF2BP3.

Keywords