title: IRF7 promotes glioma cell invasion by inhibiting AGO2 expression.
abstract: 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.
authors: Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University, Seoul, 136-713, Republic of Korea.
authors: Jun-Kyum
authors: JK
authors: Kim
authors: Xiong
authors: X
authors: Jin
authors: Seok Won
authors: SW
authors: Ham
authors: Seon Yong
authors: SY
authors: Lee
authors: Sunyoung
authors: S
authors: Seo
authors: Sung-Chan
authors: SC
authors: Kim
authors: Sung-Hak
authors: SH
authors: Kim
authors: Hyunggee
authors: H
authors: Kim
mesh_terms: D060565:Argonaute Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D063646:Carcinogenesis / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000096:biosynthesis* / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; C494234:IRF7 protein, human; D050839:Interferon Regulatory Factor-7; D035683:MicroRNAs