title: Associations between microRNA expression and mesenchymal marker gene expression in glioblastoma.
abstract: The subclassification of glioblastoma (GBM) into clinically relevant subtypes using microRNA (miRNA)- and messenger RNA (mRNA)-based integrated analysis has been attempted. Because miRNAs regulate multiple gene-signaling pathways, understanding miRNA-mRNA interactions is a prerequisite for understanding glioma biology. However, such associations have not been thoroughly examined using high-throughput integrated analysis. To identify significant miRNA-mRNA correlations, we selected and quantified signature miRNAs and mRNAs in 82 gliomas (grade II: 14, III: 16, IV: 52) using real-time reverse-transcriptase polymerase chain reaction. Quantitative expression data were integrated into a single analysis platform that evaluated the expression relationship between miRNAs and mRNAs. The 21 miRNAs include miR-15b, -21, -34a, -105, -124a, -128a, -135b, -184, -196a-b, -200a-c, -203, -302a-d, -363, -367, and -504. In addition, we examined 23 genes, including proneural markers (DLL3, BCAN, and OLIG2), mesenchymal markers (YKL-40, CD44, and Vimentin), cancer stem cell-related markers, and receptor tyrosine kinase genes. Primary GBM was characterized exclusively by upregulation of mesenchymal markers, whereas secondary GBM was characterized by significant downregulation of mesenchymal markers, miR-21, and -34a, and by upregulation of proneural markers and miR-504. Statistical analysis showed that expression of miR-128a, -504, -124a, and -184 each negatively correlated with the expression of mesenchymal markers in GBM. Our functional analysis of miR-128a and -504 as inhibitors demonstrated that suppression of miR-128a and -504 increased the expression of mesenchymal markers in glioblastoma cell lines. Mesenchymal signaling in GBM may be negatively regulated by miR-128a and -504.
authors: Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Xinlong
authors: X
authors: Ma
authors: Koji
authors: K
authors: Yoshimoto
authors: Yaulei
authors: Y
authors: Guan
authors: Nobuhiro
authors: N
authors: Hata
authors: Masahiro
authors: M
authors: Mizoguchi
authors: Noriaki
authors: N
authors: Sagata
authors: Hideki
authors: H
authors: Murata
authors: Daisuke
authors: D
authors: Kuga
authors: Toshiyuki
authors: T
authors: Amano
authors: Akira
authors: A
authors: Nakamizo
authors: Tomio
authors: T
authors: Sasaki
mesh_terms: D054392:Adipokines / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D000071451:Chitinase-3-Like Protein 1; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D037102:Lectins / Q000235:genetics / Q000378:metabolism; D019656:Loss of Heterozygosity; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D054392:Adipokines; D014408:Biomarkers, Tumor; C497483:CD44 protein, human; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D018960:Hyaluronan Receptors; D037102:Lectins; D035683:MicroRNAs; D012333:RNA, Messenger; D014746:Vimentin