title: MicroRNA-7-regulated TLR9 signaling-enhanced growth and metastatic potential of human lung cancer cells by altering the phosphoinositide-3-kinase, regulatory subunit 3/Akt pathway.
abstract: Recent evidence shows that microRNAs (miRNAs) contribute to the biological effects of Toll-like receptor (TLR) signaling on various cells. Our previous data showed that TLR9 signaling could enhance the growth and metastatic potential of human lung cancer cells. However, the potential role of miRNAs in the effects of TLR9 signaling on tumor biology remains unknown. In this paper, we first report that TLR9 signaling could reduce intrinsic miR-7 expression in human lung cancer cells. Furthermore, overexpression of miR-7 can significantly inhibit TLR9 signaling-enhanced growth and metastatic potential of lung cancer cells in vitro and in vivo. Notably, we identify phosphoinositide-3-kinase, regulatory subunit 3 (PIK3R3) as a novel target molecule of miR-7 in lung cancer cells by Western blotting and luciferase report assay. Further study shows that miR-7 inhibits the effects of TLR9 signaling on lung cancer cells through regulation of the PIK3R3/Akt pathway. These data suggest that miR-7 could act as a fine-tuner in regulating the biological effects of TLR9 signaling on human lung cancer cells, which might be helpful to the understanding of the potential role of miRNAs in TLR signaling effects on tumor biology.
authors.affiliation: Department of Immunology, Zunyi Medical College, Guizhou 563000, China Department of Medical Physics, Zunyi Medical College, Guizhou 563000, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Zhenke
authors.initials: Z
authors.lastname: Wen
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhou
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Liu
authors.forename: Qinchuan
authors.initials: Q
authors.lastname: Li
authors.forename: Guangru
authors.initials: G
authors.lastname: Fei
authors.forename: Junmin
authors.initials: J
authors.lastname: Luo
authors.forename: Tao
authors.initials: T
authors.lastname: Ren
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009362:Neoplasm Metastasis; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051217:Toll-Like Receptor 9 / Q000235:genetics* / Q000378:metabolism / Q000819:agonists; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D035683:MicroRNAs; D009838:Oligodeoxyribonucleotides; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051217:Toll-Like Receptor 9; C526902:CpG ODN 2216; C549242:MIRN7-1 microRNA, human; C495371:TLR9 protein, human; C523442:PIK3R3 protein, human