Downregulation of miR‐101 in gastric cancer correlates with cyclooxygenase‐2 overexpression and tumor growth

Abstract

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. MicroRNAs (miRNAs) 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 miR-101 for treatment of gastric cancer. Our results showed that miR-101 levels in gastric cancer tissues were significantly lower than those in the matched normal tissue (P < 0.01). Furthermore, lower levels of miR-101 were associated with increased tumor invasion and lymph node metastasis (P < 0.05). We also found an inverse correlation between miR-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-miR-101-infected gastric cancer cells. One possible mechanism of interaction is that miR-101 inhibited COX-2 expression by directly binding to the 3′-UTR of COX-2 mRNA. Overexpression of miR-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 miR-101 may function as a tumor suppressor in gastric cancer, with COX-2 as a direct target.

MicroRNA-101 Inhibits Cell Proliferation, Invasion, and Promotes Apoptosis by Regulating Cyclooxygenase-2 in Hela Cervical Carcinoma Cells

“…Substantial evidence has shown unregulated COX-2 expression to be a contributing factor in many chronic diseases and cancer (Menter et al, 2010). Many studies have confirmed, COX-2 gene has a closely relation with variety of human tumors in the occurrence and development , such as gastric cancer (He et al, 2012), breast cancer (Hsia et al, 2013), colorectal neoplasia (Dixon et al, 2013), etc. Furthermore ,The many current researchs also showed that between COX-2 and microRNAs exist certain relationship, or even co-regulated to the tumor incidence.…”

Paclitaxel combined with harmine inhibits the migration and invasion of gastric cancer cells through downregulation of cyclooxygenase-2 expression

“…The aim of the present study was to evaluate whether the combination of PTX and HM exerted synergistic antitumor effects on the migration and invasion of two human gastric cancer cell lines, SGC-7901 and MKN-45, in which COX-2 is known to be expressed (13). In addition, the present study aimed to explore the possible mechanism by which this effect may proceed.…”

Harmine combined with paclitaxel inhibits tumor proliferation and induces apoptosis through down-regulation of cyclooxygenase-2 expression in gastric cancer

“…Untreated cells in serum-free medium were used as controls. After incubation for 48 h at 37˚C, the cell proliferation was determined by the MTT assay as described in our previous study (15).…”

“…In the present study, a human gastric cancer cell line SGC-7901, in which COX-2 was expressed (15), was selected to examine whether PTX in combination with HM exerts synergistic anti-tumor effects on human gastric cancer cells in vitro and in vivo and to further explore the probable mechanism.…”