Abstract
MicroRNAs (miRs) are short endogenous non-coding RNAs that act as posttranscriptional regulatory factors of gene expression. Downregulation of miR-1 has been reported in gastric cancer; however, the mechanisms underlying its functions via target genes in gastric cancer remain largely unknown. The purpose of this study was to investigate the mechanism by which miR-1 inhibits gastric cancer cell proliferation and migration. The effects of miR-1 on gastric cancer cell proliferation and migration were determined by MTT and wound-healing assays. Cell protein expression of the miR-1 target gene MET was analyzed by Western blotting. Finally, MET expression was evaluated by immunohistochemistry in a stomach tumor tissue microarray (TMA). Ectopic expression of miR-1 inhibited proliferation and migration in both AGS and SGC-7901 gastric cancer cell lines. miR-1 directly targets the MET gene and downregulates its expression. MET siRNA also inhibited proliferation and migration in both cell lines. Immunohistochemistry revealed significantly higher MET expression levels in gastric cancer tissues compared with matched adjacent non-cancer tissues. These findings indicate that the miR-1/MET pathway is a potential therapeutic target due to its crucial role in gastric cancer cell proliferation and migration.
Highlights
Gastric cancer is the fourth most common malignancy worldwide
Ectopic expression of miR-1 inhibits gastric cancer cell proliferation and motility in vitro results indicated that overexpression of miR-1 inhibited proliferation of gastric cancer cells in a dose-dependent manner in vitro (Fig. 1)
The results showed that the two gastric cancer cell lines were significantly inhibited in miR-1 transfectants in comparison with cells transfected with the non-specific miR negative control (Fig. 1c, d)
Summary
Gastric cancer is the fourth most common malignancy worldwide. It is more common in men and in developing countries, including East Asian and Eastern European nations. There were approximately 700,000 gastric cancer deaths in 2012, making this malignancy the third leading cause of cancer death after lung and liver cancers [1, 2]. Treatment of stomach cancer may include surgery, adjuvant chemotherapy, and/or radiation therapy. Despite the demonstrated benefits of these treatments, gastric cancer remains virtually incurable with the metastatic disease. It is urgent to improve the overall survival rate of patients with gastric cancer by identifying novel therapeutic strategies
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