ABSTRACT. We aimed to investigate the biological role of miR-367 in uveal melanoma cell growth and migration, and the underlying mechanism responsible. Quantitative real-time polymerase chain reaction was performed to evaluate miR-367 expression in uveal melanoma tissue samples and cell lines. A miR-367 mimic, miR-367 inhibitor, and negative control oligonucleotide were transfected into these cells to investigate the function of this microRNA. In addition, the role of PTEN in miR-367-mediated uveal melanoma cell growth and migration was evaluated. miR-367 was significantly upregulated in uveal melanoma cells and tissue samples (both P < 0.01). Its inhibition suppressed the proliferation, cell cycle transition, and migration of such cells, and increased levels had the opposite effect. PTEN was confirmed to be a target gene of miR-367. More importantly, co-transfection with a PTEN construct lacking the 3'-untranslated region mitigated miR-367 mimic-induced promotion of uveal melanoma cell proliferation and migration. In summary, miR-367 was found to be upregulated in this malignancy, and may promote uveal melanoma cell proliferation and migration, at least in part by regulating PTEN.

DNA hypomethylation may activate oncogene transcription, thus promoting carcinogenesis and tumor development. S-adenosylmethionine (SAM) is a methyl donor in numerous methylation reactions and acts as an inhibitor of intracellular demethylase activity, which results in hypermethylation of DNA. The main objectives of this study were to determine whether DNA hypomethylation correlated with vascular endothelial growth factor-C (VEGF-C) expression, and the effect of SAM on VEGF-C methylation and gastric cancer growth inhibition. VEGF-C expression was assayed by Western blotting and RT-qPCR in gastric cancer cells, and by immunohistochemistry in tumor xenografts. VEGF-C methylation was assayed by bisulfite DNA sequencing. The effect of SAM on cell apoptosis was assayed by flow cytometry analyses and its effect on cancer growth was assessed in nude mice. The VEGF-C promoters of MGC-803, BGC-823, and SGC-7901 gastric cancer cells, which normally express VEGF-C, were nearly unmethylated. After SAM treatment, the VEGF-C promoters in these cells were highly methylated and VEGF-C expression was downregulated. SAM also significantly inhibited tumor growth in vitro and in vivo. DNA methylation regulates expression of VEGF-C. SAM can effectively induce VEGF-C methylation, reduce the expression of VEGF-C, and inhibit tumor growth. SAM has potential as a drug therapy to silence oncogenes and block the progression of gastric cancer.