Downregulation of CircRNA CDR1as specifically triggered low-dose Diosbulbin-B induced gastric cancer cell death by regulating miR-7-5p/REGγ axis

Abstract

Diosbulbin-B (DB) was the main compound of Dioscorea bulbifera L, which was widely used for cancer treatment in Asia. However, the hepatotoxicity induced by high-dose DB seriously limited its possibility using for gastric cancer (GC) treatment in clinic. In this study, we found that DB inhibited GC cells and hepatocytes cell viability in a dose- and time-dependent manner. Specifically, high-dose DB (50μM) significantly inhibited cell proliferation and promoted cell apoptosis, while low dose DB (12.5μM) had little effects on cell viability. Besides, high-dose DB (50μM) significantly decreased CircRNA CDR1as levels in gastric cancer cells instead of hepatocytes. Notably, knock-down of CircRNA CDR1as triggered low-dose DB (12.5μM) induced GC cell death, but had little effects on hepatocytes proliferation and apoptosis. Further results showed that CircRNA CDR1as increased REGγ expressions in GC cells by sponging miR-7-5p, and high-dose DB (50μM) increased miR-7-5p levels and inhibited REGγ expressions in GC cells instead of hepatocytes. In addition, either downregulated miR-7-5p or overexpressed REGγ reversed the promoting effects of downregulated CircRNA CDR1as on low-dose DB-induced GC cell death. Taken together, we concluded that knock-down of CircRNA CDR1as specifically promoted the cytotoxic effects of low-dose DB on GC cells instead of hepatocytes by regulating miR-7-5p/REGγ axis.