miR-129-3p inhibits NHEJ pathway by targeting SAE1 and represses gastric cancer progression

Gastric cancer (GC) is one of the leading malignancies worldwide and is also a leading cause of cancer-related mortality. Micro RNA (miRNA) is a group of short non-coding RNAs modulating gene expression through targeting the 3'UTR of genes. Peripheral blood exosome miRNAs are relatively stable and might be used as biomarkers for clinical diagnosis. In this study, we found a reduced level of miR-129-3p in GC tumor when compared with adjacent non-tumor tissues, and the peripheral blood exosome miR-129-3p level was also reduced when compared with healthy controls. Subsequently, we identified that miR-129-3p repressed the expression of SUMO-activating enzyme subunit 1 (SAE1) directly through targeting 3'UTR. miR-129-3p also inhibited the sumoylation modification of XRCC4 which disturbed the nuclear localization of XRCC4 and induced more DNA damage in GC cells. Furthermore, overexpression of miR-129-3p induced more cell apoptosis and inhibited GC cell proliferation, migration and invasion, indicating miR-129-3p is a powerful anti-tumor miRNA and has potential for GC treatment.