title: Inhibition of the Hedgehog signaling pathway suppresses cell proliferation by regulating the Gli2/miR-124/AURKA axis in human glioma cells.
abstract: Multiple lines of evidence indicate that aberrant activation of Hedgehog (Hh) signaling plays an important role in tumorigenesis in human glioma. However, the underlying molecular mechanism and crucial downstream targets of glioma-associated oncogene (Gli), a primary transcriptional regulator of Hh signaling, are not fully understood. Here, we report the identification of miR-124 as a novel downstream target of the transcriptional factor Gli2, which is important for proliferation and tumor growth in human glioma cells. Blockade of Hh signaling leads to a remarkable increase in miR-124 expression in glioma cells, whereas overexpression of Gli2 suppresses miR-124 expression by increasing the direct binding of Gli2 to the upstream region of the transcriptional start site for miR-124. Furthermore, we found that miR-124 potentially interacts with the 3'-UTR region of AURKA. Overexpression of miR-124 significantly decreased the expression of AURKA in glioma cells. In contrast, the loss of miR-124 led to the increased expression of AURKA mRNA and protein. In addition, cell proliferation and colony formation ability were significantly decreased following Gli2 knockdown in human glioma cells, while transfection with a miR-124 inhibitor rescued the proliferative ability of cells. These results demonstrate that miR-124 is an important downstream target gene of Hh signaling, and the Gli2/miR-124/AURKA axis is essential for the proliferation and growth of human glioma cells.
authors.affiliation: Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Liyao
authors.initials: L
authors.lastname: Xu
authors.affiliation: Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.affiliation: MOE Key Laboratory of Bioinformatics, School of Life Science, Tsinghua University, Beijing 100084, P.R. China.
authors.forename: Zhangming
authors.initials: Z
authors.lastname: Yan
authors.affiliation: MOE Key Laboratory of Bioinformatics, School of Life Science, Tsinghua University, Beijing 100084, P.R. China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Shiwen
authors.initials: S
authors.lastname: Luo
authors.affiliation: Department of Biostatistics and Epidemiology, School of Public Health, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Quqin
authors.initials: Q
authors.lastname: Lu
mesh_terms: D064096:Aurora Kinase A / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics; D000075746:Zinc Finger Protein Gli2
chemical_list: C082593:GLI2 protein, human; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D014157:Transcription Factors; D000075746:Zinc Finger Protein Gli2; C576917:AURKA protein, human; D064096:Aurora Kinase A