Micro RNA ‐148a is downregulated in gastric cancer, targets MMP 7, and indicates tumor invasiveness and poor prognosis

Gastric cancer ( GC ) develops through deregulation of gene expression and accumulation of epigenetic abnormalities, leading to tumor cell acquisition of malignant features. Micro RNA s (mi RNA s) play a critical role in cancer development where they can act as oncogenes or oncosuppressors. To identify mi RNA s that are associated with some clinicopathologic features of GC and/or participate in tumor progression, mi RNA expression in 20 GC tissues and five corresponding non‐neoplastic gastric mucosa was examined by mi RNA microarray. Oligonucleotide array analysis was carried out for mi RNA target prediction. The functions of candidate mi RNA s and their target genes were also analyzed by quantitative RT ‐ PCR , Western blotting, reporter gene assay, and cell invasion assay. Comparison of mi RNA 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 MMP 7 expression was markedly downregulated in miR‐148a‐overexpressing GC cells; MMP 7 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 MMP 7 expression.