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.

Meteorin‐like (Metrnl) is a novel adipokine that is highly expressed in white adipose tissue. Metrnl stimulates energy expenditure and improves glucose tolerance in rodents. However, whether Metrnl plays a role in coronary artery disease (CAD) remains to be elucidated. The present study aimed to investigate the association of serum Metrnl with CAD in Chinese patients. A total of 193 patients with CAD and 156 control subjects were enrolled in this study. Serum Metrnl concentration was measured by enzyme‐linked immunosorbent assay. Anthropometric phenotypes, fasting glucose, serum lipids, and inflammatory cytokines were measured. Serum Metrnl was lower in CAD patients when compared to those controls (132.41 vs 173.17 pg/mL, P < 0.001). Serum Metrnl was negatively correlated with metabolic parameters, including body mass index, total cholesterol, and low‐density lipoprotein cholesterol as well as inflammatory markers including high‐sensitivity C‐reactive protein, IL‐1β, and IL‐11 even after adjustment for potential confounding variables (P < 0.05). In multivariable logistic regression analyses, compared to those in the highest tertile of serum Metrnl levels, subjects in the lowest tertile had the highest risks for CAD (adjusted OR = 2.63, 95% CI = 1.46‐4.27, P = 0.001). After adjustment for potential confounding variables, serum Metrnl was also decreased as the number of stenosed vessels increased (P < 0.001). Furthermore, decreased Metrnl level was negatively correlated with the severity of CAD quantified by the Gensini score. This first case‐control study shows significant associations of serum Metrnl with the presence and severity of CAD, suggesting Metrnl might be a new promising therapeutic target for CAD.

Although platinum-based chemotherapies have long been used as standard treatment in ovarian cancer, cisplatin resistance is a major problem that restricts its use. Herein, we investigate the biological function of SLC27A2 and its underlying mechanisms in regulating chemo-resistance in ovarian cancer. The findings show that SLC27A2 down-regulation in primary ovarian cancer tissues correlates with chemo-resistance and poor patient survival in our patient cohort. Significantly, we demonstrate that up-regulation of SLC27A2 by lentivirus-mediated p-SLC27A2 sensitizes ovarian cancer cells to cisplatin in vitro and in vivo via apoptosis. Mechanistic investigation reveals that miR-411 is the most strikingly over-expressed gene in response to ectopic expression of SLC27A2, but under-expressed in recurrent ovarian cancer tissues. Lower miR-411 expression contributes to ovarian cancer chemo-resistance in vitro and in vivo. Furthermore, SLC27A2 directly binds specific sites in the miR-411 promoter region and promoter activity decreases after mutation of putative SLC27A2-binding sites. This indicates that SLC27A2 is required for the transcriptional induction of miR-411. The luciferase assays also confirm that miR-411 directly targets ABCG2 in ovarian cancer, and overall findings establish the SLC27A2-miR-411-ABCG2 pathway in the regulation of ovarian cancer chemo-resistance with potential therapeutic applications.

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