Expression and Clinical Significance of miR-181d in Serum and PDCD4 in Gastric Cancer Patients

Objective To investigate miR-181d and PDCD4 expression in the serum of gastric cancer(GC) patients and regulatory mechanism.

Methods The expression of miR-181d and PDCD4 were detected in 6 gastric cell lines using Real-time PCR and Western blot. Real-time PCR was used to detect miR-181d expression in serum of 58 GC patients and 50 healthy volunteers, and the protein level of PDCD4 was detected by ELISA assay. Furthermore, the experiment of siRNA or mimics was used to evaluate the role of miR-181d on the regulation of PDCD4 in GC cells, and we constructed the PDCD4 3'-UTR luciferase report vector to analyze the association between miR-181d and PDCD4.

Results miR-181d and PDCD4 were differentially expressed in GC cell lines; miR-181d in the serum of GC patients was higher than that in normal group (P < 0.001), while the expression of PDCD4 protein in GC patients was decreased (P < 0.05). It was found that there was a significant inverse correlation between miR-181d and PDCD4 expression in GC patients (R²=-0.44) and also in normal group(R²=-0.426). ROC curve analysis showed that miR-181d and PDCD4 had good specificity and sensitivity for the diagnosis of GC and normal population in vitro. Moreover, miR-181d expression was associated with smoking and drinking history, respectively (P=0.015, P=0.034). The expression of PDCD4 was only associated with drinking history(P < 0.001). Overexpression of miR-181d in AGS cells decreased the expression of PDCD4, and the expression of PDCD4 was increased after transfection with antisense miR-181d in BGC823 cells. Luciferase reporter system results suggested that miR-181d could bind to the 3'-UTR region of PDCD4.

Conclusion Elevated miR-181d expression and downregulated PDCD4 expression are detected in the serum of GC patients; miR-181d may mediate PDCD4 expression in the development of gastric cancer.