MiR-300 Alleviates Cell Proliferation and Migration and Facilitates Cell Apoptosis by Targeting c-Met in Gastric Cancer

Abstract

c-Met is a potent oncogene, whose aberrant activation has not been fully clarified. In this study, we discover the biological function of miR-300 in gastric cancer (GC) carcinogenesis and the underlying mechanism. The overexpression, oncogenic functions, and survival analysis of c-Met in GC tissues and cells were firstly determined. miRNAs that potentially targets c-Met were then predicted by bioinformatics. The expression levels of candidate miR-300 in GC tissue pairs were investigated. Pearson analysis revealed a negative relation between miR-300 and c-Met expressions. miR-300 and c-Met expression levels were determined in three GC cell lines (MKN-45, SGC-7901, and AGS) as well. Reduced miR-300 led to increase c-Met levels. Luciferase report assay demonstrated a direct binding site of miR-300 in the 3’ untranslated region (3 ${}^{\prime }$ UTR) of c-Met. Finally, the regulatory role of miR-300 on MKN-45 cells was studied by cell proliferation, migration, and apoptosis assays. Overexpression of miR-300 attenuated viability and migration and accelerated apoptosis in MKN-45. We also induced a rescue experiment with c-Met overexpression plasmid and finally proved that miR-300 exerted a suppressing role on MKN-45 proliferation and migration but promoted MKN-45 apoptosis by directly inhibiting c-Met. This study provides a novel insight into the targeted drug development for GC therapies.