MicroRNA-148a is downregulated in gastric cancer, targets MMP7, and indicates tumor invasiveness and poor prognosis.
Bottom Line: 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.
Affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.Show MeSH
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Mentions: To investigate the biological significance of miR-148a in GC, we carried out an MTT assay 4 days after altering miR-148a expression. In this experiment, we used MKN-1 cells transfected with miR-148a precursor and HSC-57 cells transfected with miR-148a inhibitor. MKN-1 and HSC-57 were selected as they possessed the lowest and highest endogenous miR-148a expression among nine GC cell lines, respectively. Successful overexpression and suppression of miR-148a in each treated cell line were confirmed by qRT-PCR (Fig. 2a). Cell growth of GC cells with deregulated miR-148a expression did not differ from that of cells transfected with control miRNA up to day 4 (data not shown). Next, a Transwell invasion assay was carried out. The invasiveness of miR-148a-overexpressing MKN-1 cells was reduced compared with the negative control miRNA-transfected MKN-1 cells (Fig. 2b). In contrast, the invasiveness of miR-148a-suppressed HSC-57 cells was greater than that of the negative control miRNA-transfected HSC-57 cells (Fig. 2c). These results are consistent with those of a previous report,(22) and indicate that miR-148a regulates some genes which in turn affect tumor invasion in GC cells.
Affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.