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

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

JOURNAL=Frontiers in Oncology

VOLUME=Volume 10 - 2020

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.574001

DOI=10.3389/fonc.2020.574001

ISSN=2234-943X

ABSTRACT=Ionizing radiation is one of the common environmental carcinogens. miRNAs play critical roles in the processes of tumor occurrence, development, metastasis and miRNA generation. However, the relationship between radiation-induced carcinogenesis and miRNA is rarely reported. This study is aimed to investigate the effect of miRNAs on radiation-induced carcinogenesis. By using miRNA array and prediction for miRNAs target genes, a miRNA-mRNA crosstalk network was established. With this network, a critical miRNA that was involved in the radiation-induced carcinogenesis could be identified. Subsequently the function of this critical miRNA was confirmed by using knockout mice and cellular experiments. As a result, by the miRNA-mRNA crosstalk network, miR-486 was identified as one of the most down-regulated miRNAs in radiation-induced thymic lymphoma tissues compared to normal tissues. miR-486 is involved in the development of radiation-induced thymic lymphoma and inhibited 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