Abstract
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.
Highlights
Carcinogenesis could be induced by environmental factors which mainly include physical, chemical, and biological factors, and ionizing radiation is one of the common physical carcinogens [1,2,3]
MiR-486 Inhibits Tumorigenesis carcinogenesis has been studied in our lab since 1999, and we successfully established a radiation-induced thymic lymphoma (RTL) mice model by using fractionated irradiation
The results showed that both MUT1 and MUT2 could weaken the inhibition of miR-48 to IGF2BP3 3 ‘UTR region, and MUT1 was stronger than MUT2 (Figure 4I), which indicated that miR-486 plays a role by inhibiting both two complementary sequences (896-903bp and 928-934bp) in the 3 ‘UTR region of IGF2BP3
Summary
Carcinogenesis could be induced by environmental factors which mainly include physical, chemical, and biological factors, and ionizing radiation is one of the common physical carcinogens [1,2,3]. MiR-486 Inhibits Tumorigenesis carcinogenesis has been studied in our lab since 1999, and we successfully established a radiation-induced thymic lymphoma (RTL) mice model by using fractionated irradiation. Using this model, a series of studies have been conducted on the mechanism of radiation-induced carcinogenesis [7]. MiRNAs play critical roles in the processes of tumor occurrence, development, metastasis, and miRNA generation [8, 9]. The relationship between radiation-induced carcinogenesis and miRNA expression is rarely revealed.
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