circRNA circSCAF8 promotes tumor growth and metastasis of gastric cancer by miR-1293/TIMP1signaling

AbstractSCAF8 (SR-like CTD-associated factor 8) can regulate transcriptional termination, but the function of circSCAF8 is still unclear. In our study, we found circSCAF8 expression was significantly increased in gastric cancer, especially in gastric cancer tissues with lymph node metastasis. Kaplan-Meier curve indicated high circSCAF8 expression group possessed low overall survival time in gastric cancer. Moreover, circSCAF8 shRNA viruses could decrease gastric cancer proliferation, invasion, and migration in vitro. By using bioluminescence imaging (BLI) technology in vivo experiments, we also found circSCAF8 shRNA viruses could inhibit the growth of xenograft tumors and gastric cancer lung metastasis. RIP and circRNA pulldown assays confirmed circSCAF8 could directly bind to miR-1293, but circSCAF8 could not regulate the expression of miR-1293 in gastric cancer. Interestingly, the downstream gene TIMP1 of miR-1293 could be regulated by circSCAF8, and this view was further verified in gastric cancer tissues. Moreover, we confirmed that miR-1293 could directly inhibit TIMP1 expression. Subsequently, through rescue experiments, we found TIMP1 overexpression could reverse the effect of circSCAF8 shRNA viruses on gastric cancer. In conclusion, circSCAF8 expression was increased in gastric cancer, and circSCAF8 shRNA viruses could inhibit gastric cancer growth and metastasis by elevating TIMP1 expression via miR-1293.