MicroRNA-122 inhibits proliferation and invasion in gastric cancer by targeting CREB1

摘要

MicroRNA-122 (miR-122) has been implicated in tumor development and progression in various types of cancers. However, the biological function and regulatory mechanisms of miR-122 in gastric cancer (GC) remain largely unknown. We aimed to determine the biological role and underlying mechanism of miR-122 in GC. Real time quantitative RT-PCR (qRT-PCR) was performed to detect the expression of miR-122 in GC tissues and cell lines. CCK8, wound healing, and transwell assays were conducted to determine the effect of miR-122 on cell proliferation, migration, and invasion, respectively. Target molecules were identified by luciferase activity, quantitative RT-PCR, and western blotting. We found that miR-122 expression was significantly decreased in both GC tissues and cell lines and that reduced expression was significantly associated with aggressive clinicopathological features in patients. We also found that overexpression of miR-122 markedly inhibited proliferation, migration, and invasion in GC cell lines. In addition, cAMP responsive element binding protein 1 (CREB1) was identified as a direct target of miR-122, and its expression was negatively correlated with miR-122 expression in GC tissues (r = -0.711, P < 0.001). CREB1overexpression rescued the suppressive effect of miR-122 on GC cell proliferation, migration, and invasion. Moreover, we demonstrated that miR-122 inhibited GC tumorigenesis in vivo by repressing CREB1 expression. These findings suggest that miR-122 might function as a tumor suppressor in GC and could serve as a promising candidate for therapeutic applications regarding GC treatment.