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Exp Ther Med. 2015 Aug;10(2):717-722. Epub 2015 Jun 4.

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

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1
Cancer Center, The First Hospital Affiliated to Fuzhou General Hospital of Nanjing Military Command of Chinese PLA, Putian, Fujian 351100, P.R. China.

Abstract

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.

KEYWORDS:

cell apoptosis; cell invasion; gastric carcinoma; hypoxia-inducible factor-1α; microRNA-18a

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