Downregulation of mi R-101 in gastric cancer correlates with cyclooxygenase-2 overexpression and tumor growth.

Cyclooxygenase-2 ( COX-2) plays an important role in the carcinogenesis and progression of gastric cancer. It has been demonstrated that COX-2 overexpression depends on different cellular pathways, involving both transcriptional and post-transcriptional regulation. Micro RNAs (mi RNAs) are small, noncoding RNAs that function as post-transcriptional regulators. Here, we characterize miR-101 expression and its role in the regulation of COX-2 expression, which in turn, will provide us with additional insights into the potential therapeutic benefits of exogenous mi R-101 for treatment of gastric cancer. Our results showed that mi R-101 levels in gastric cancer tissues were significantly lower than those in the matched normal tissue ( P < 0.01). Furthermore, lower levels of mi R-101 were associated with increased tumor invasion and lymph node metastasis ( P < 0.05). We also found an inverse correlation between mi R-101 and COX-2 expression in both gastric cancer specimens and cell lines. Significant decreases in COX-2 mRNA and COX-2 levels were observed in the pre-mi R-101-infected gastric cancer cells. One possible mechanism of interaction is that mi R-101 inhibited COX-2 expression by directly binding to the 3′- UTR of COX-2 m RNA. Overexpression of mi R-101 in gastric cancer cell lines also inhibited cell proliferation and induced apoptosis in vitro, as well as inhibiting tumor growth in vivo. These results collectively indicate that mi R-101 may function as a tumor suppressor in gastric cancer, with COX-2 as a direct target. [ABSTRACT FROM AUTHOR]