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MicroRNA-148a is downregulated in gastric cancer, targets MMP7, and indicates tumor invasiveness and poor prognosis.
- Source :
-
Cancer science [Cancer Sci] 2014 Feb; Vol. 105 (2), pp. 236-43. Date of Electronic Publication: 2014 Jan 06. - Publication Year :
- 2014
-
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.<br /> (© 2013 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.)
- Subjects :
- Cell Growth Processes physiology
Cell Line, Tumor
DNA Methylation
Down-Regulation
Female
Humans
Lymphatic Metastasis
Male
Matrix Metalloproteinase 7 metabolism
MicroRNAs metabolism
Middle Aged
Neoplasm Invasiveness
Prognosis
Stomach Neoplasms metabolism
Matrix Metalloproteinase 7 genetics
MicroRNAs genetics
Stomach Neoplasms genetics
Stomach Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1349-7006
- Volume :
- 105
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cancer science
- Publication Type :
- Academic Journal
- Accession number :
- 24283384
- Full Text :
- https://doi.org/10.1111/cas.12330