microRNA-18a regulates gastric carcinoma cell apoptosis and invasion by suppressing hypoxia-inducible factor-1α expression.

Hypoxia is associated with various pathophysiological events, including cancer, lung and cardiovascular diseases. A number of studies have indicated that alterations in microRNA (miRNA) expression may be involved in the regulation of the cellular response to hypoxia. In the present study, miR-18a expression was revealed to be markedly downregulated under hypoxic conditions in MGC-803 and HGC-27 gastric carcinoma cell lines. Furthermore, miR-18a was demonstrated to affect the rate of cell apoptosis and the cell invasion ability in MGC-803 and HGC-27 cells under hypoxic conditions. Cell apoptosis was were analyzed using flow cytometry and cell invasiveness was evaluated using a Transwell-matrigel assay. The results showed that miR-18a overexpression was able to promote cell apoptosis and inhibit cell invasion. Using bioinformatic analysis, hypoxia-inducible factor (HIF)-1α was identified as one of the target genes of miR-18a, and based on the function of HIF-1α in hypoxia, miR-18a was predicted to regulate HIF-1α expression. This hypothesis was confirmed by a further luciferase assay and the detection of the mRNA and protein expression levels of HIF-1α following the induction of miR-18a overexpression. In addition, the expression levels of mitochondrial apoptosis-associated genes were detected following the induction of miR-18a overexpression. In the cells overexpressing miR-18a, the Bcl-2 protein expression level was downregulated, while the protein expression levels of Bax, caspase 3 and caspase 9 were upregulated in the MGC-803 and HGC-27 cell lines. Therefore, miR-18a was hypothesized to induce apoptosis through the HIF-1α/mitochondrial apoptosis pathway.