IRF7 promotes glioma cell invasion by inhibiting AGO2 expression
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Interferon regulatory factor 7 (IRF7) is the master transcription factor that plays a pivotal role in the transcriptional activation of type I interferon genes in the inflammatory response. Our previous study revealed that IRF7 is an important regulator of tumor progression via the expression of inflammatory cytokines in glioma. Here, we report that IRF7 promotes glioma invasion and confers resistance to both chemotherapy and radiotherapy by inhibiting expression of argonaute 2 (AGO2), a regulator of microRNA biogenesis. We found that IRF7 and AGO2 expression levels were negatively correlated in patients with glioblastoma multiforme. Ectopic IRF7 expression led to a reduction in AGO2 expression, while depletion of IRF7 resulted in increased AGO2 expression in the LN-229 glioma cell line. In an in vitro invasion assay, IRF7 overexpression enhanced glioma cell invasion. Furthermore, reconstitution of AGO2 expression in IRF7-overexpressing cells led to decreased cell invasion, whereas the reduced invasion due to IRF7 depletion was rescued by AGO2 depletion. In addition, IRF7 induced chemoresistance and radioresistance of glioma cells by diminishing AGO2 expression. Finally, AGO2 depletion alone was sufficient to accelerate glioma cell invasion in vitro and in vivo, indicating that AGO2 regulates cancer cell invasion. Taken together, our results indicate that IRF7 promotes glioma cell invasion and both chemoresistance and radioresistance through AGO2 inhibition.
KeywordsGlioblastoma IRF7 AGO2 Invasion Chemoresistance Radioresistance
We would like to thank all members of the Cell Growth Regulation Laboratory for the helpful discussion and technical assistance. This work was supported by the National Nuclear Technology Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT and Future Planning (no. 2013M2A2A7042530 to H. Kim) and the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (no. 2011–0024089 to S.-H. Kim). S.W. Ham was supported by a Kwanjeong Educational Foundation Domestic Scholarship.
Conflicts of interest
The authors declare that they have no conflict of interest.
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