miR-483 is down-regulated in gastric cancer and suppresses cell proliferation, invasion and protein O-GlcNAcylation by targeting OGT

Fei-Yue Yu,  Chuan-Yi Zhou, Ya-Bing Liu, Bing Wang, Lei Mao, Yang Li

Abstract:

MicroRNAs (miRNAs) are involved in the gastric carcinogenesis and progression. Here, we confirmed that miR-483 was frequently decreased in gastric cancer patients. The expression levels of miR-483 were negatively correlated with tumor stage, node metastasis and stromal invasion. Log-rank tests demonstrated that low expression of miR-483 was strongly correlated with poor overall survival in patients with gastric cancer. Moreover, ectopic expression of miR-483 remarkably suppressed gastric cancer cell proliferation by enhancing cell apoptosis and significantly inhibited the invasion of gastric cancer cells, while low expression of miR-483 exhibited the opposite effect. Bioinformatics analysis revealed that OGT was a potential target of miR-483, and miR-483 inhibited the expression level of OGT mRNA by direct binding to its 3'-untranslated region (3'UTR). Expression of miR-483 was negatively correlated with OGT in gastric cancer tissues. In addition, modulation of miR-483 expression could affect the global cellular protein O-GlcNAcylation in gastric cancer cells. Furthermore, silencing of OGT counteracted the effects of miR-483 repression, while its overexpression reversed tumor inhibitory effects of miR-483. In conclusion, our study revealed that miR-483 functions as a tumor suppressor by inhibiting proliferation, invasion and protein O-GlcNAcylation of gastric cancer via targeting OGT, and that miR-483 may serve as prognostic or therapeutic target for gastric cancer.