title: MicroRNA-148a is downregulated in gastric cancer, targets MMP7, and indicates tumor invasiveness and poor prognosis.
abstract: Gastric cancer (GC) develops through deregulation of gene expression and accumulation of epigenetic abnormalities, leading to tumor cell acquisition of malignant features. MicroRNAs (miRNAs) play a critical role in cancer development where they can act as oncogenes or oncosuppressors. To identify miRNAs that are associated with some clinicopathologic features of GC and/or participate in tumor progression, miRNA expression in 20 GC tissues and five corresponding non-neoplastic gastric mucosa was examined by miRNA microarray. Oligonucleotide array analysis was carried out for miRNA target prediction. The functions of candidate miRNAs and their target genes were also analyzed by quantitative RT-PCR, Western blotting, reporter gene assay, and cell invasion assay. Comparison of miRNA expression profiles revealed that downregulation of miR-148a was identified in most of the GC tissues. Downregulation of miR-148a was significantly correlated with an advanced clinical stage, lymph node metastasis, and poor clinical outcome. Custom oligonucleotide array analysis revealed that MMP7 expression was markedly downregulated in miR-148a-overexpressing GC cells; MMP7 was found to be a direct and functional target of miR-148a, participating in cell invasion. These results suggest that miR-148a contributes to the maintenance of homeostasis in normal stomach tissue and plays an important role in GC invasion by regulating MMP7 expression.
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Naito
authors.forename: Naohide
authors.initials: N
authors.lastname: Oue
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sentani
authors.forename: Naohiro
authors.initials: N
authors.lastname: Uraoka
authors.forename: Htoo Zarni
authors.initials: HZ
authors.lastname: Oo
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Aoyagi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sasaki
authors.forename: Wataru
authors.initials: W
authors.lastname: Yasui
mesh_terms: D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
chemical_list: C550570:MIRN148 microRNA, human; D035683:MicroRNAs; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7
keywords: Gastric cancer; MMP7; cancer invasion; miR-148a; microRNA