MicroRNA-128 contributes to the progression of gastric carcinoma through GAREM-mediated MAPK signaling activation

Gastric carcinoma (GC) represents the most common malignant cancer and the second leading cause of cancer death worldwide. However, the molecular mechanisms and biological progression of GC remain unknown. In this study, we found that miR-128 is a critical tumor suppressor that is downregulated in GC patients and GC cells and that GAREM is a direct downstream target of miR-128. Overexpression of miR-128 in HGC-27 and MKN-45 cells resulted in suppressed cell growth and promoted cell apoptosis through a GAREM-dependent mechanism. Moreover, the precise mechanisms underlying the antitumor effect of miR-128 in GC are at least partially due to suppressing activation of the MAPK signaling pathway, induced by suppressing GAREM expression. This study is the first to demonstrate that the miR-128-GAREM-MAPK signaling pathway forms a critical feedback loop and mediates GC development, and these findings might demonstrate a potential therapeutic strategy for GC.