Deficiency of microRNA-628-5p promotes the progression of gastric cancer by upregulating PIN1.

ABSTRACT

Gastric cancer is one of the most common cancer and is the second leading cause of cancer-related mortality in the world. PIN1, belonging to peptidyl-prolyl cis-trans isomerase family, uniquely catalyzes the structural transformation of phosphorylated Ser/Thr-Pro motif. It's high expressed in most cancers and promotes their progression. However, the mechanism of PIN1 high expression and its function in gastric cancer progression are still unclear. In this research, we revealed that PIN1 not only promotes the proliferation and colony formation of gastric cancer, but also increases its migration and invasion. The PIN1 expression in metastasis lesion is usually higher than the corresponding primary site. Inhibiting PIN1 by shRNA suppresses the progression of gastric cancer significantly. Besides, we demonstrated that miR-628-5p is a novel PIN1-targeted microRNA, and the expression of miR-628-5p is negatively correlated with PIN1 in gastric cancer. Exogenous expression of miR-628-5p inhibits the progression of gastric cancer that revered by restoring PIN1 expression. However, miR-628-5p is downregulated in majority of gastric cancer tissue especially in metastasis lesion. The lower miR-628-5p level indicates poorer prognosis. In summary, our study demonstrated that deficient miR-628-5p expression facilitates the expression of PIN1, and consequently promotes the progression of gastric cancer.