Mechanisms of MicroRNA Deregulation and MicroRNA Targets in Gastric Cancer.

Gastric cancer is a genetically heterogeneous disease that causes cancer-related deaths worldwide. Although many studies on this disease have been performed, the molecular mechanisms of gastric tumorigenesis, invasion, and metastasis have still not been identified. MicroRNAs (miRNAs) are endogenously coded small RNA molecules, 18-25 nucleotides in length, that regulate gene expression at the post-transcriptional level. They are required for physiological activities in the cell, including development, proliferation, differentiation, and apoptosis. Research has now indicated their importance in carcinogenesis, with miRNA profiling revealing differences in the tumor and the normal tissue in several cancers. This difference in the expression pattern might lead to disrupted regulation of genes such as tumor suppressor genes and proto-oncogenes that are involved in cell cycle control, proliferative pathways, apoptosis, and metastasis in gastric carcinogenesis. Genes encoding miRNAs have been characterized as novel proto-oncogenes and tumor-suppressor genes based on findings that these miRNAs control malignant phenotypes. miRNA deregulation promotes cell-cycle progression, confers resistance to apoptosis, and enhances invasiveness and metastasis. Deregulated miRNAs affect the regulation of their target genes. Knowing the targets of miRNAs is of great importance for identifying the molecular mechanisms behind gastric carcinogenesis and forms the focus of this review.