Circ_0000190 sponges miR-382-5p to suppress cell proliferation and motility and promote cell death by targeting ZNRF3 in gastric cancer.

Abstract

This study was to explore the role of circRNA_0000190 (circ_0000190) in gastric cancer (GC) progression. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were applied to measure RNA and protein expression. 5-Ethynyl-2'-deoxyuridine (EdU) assay and cell counting kit-8 (CCK8) assay were implemented to analyze cell proliferation ability. Transwell assays were conducted to analyze cell motility. Cell ferroptosis was assessed using commercial kit. The target relationship between microRNA-382-5p (miR-382-5p) and circ_0000190 or zinc and ring finger 3 (ZNRF3) was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Murine xenograft model was used to analyze the function of circ_0000190 in GC progression in vivo. Circ_0000190 was down-regulated in GC tissues and cell lines. Low expression of circ_0000190 predicted dismal prognosis in GC patients. Circ_0000190 overexpression inhibited the proliferation, migration and invasion and promoted Erastin- or ras selective lethal 3 (RSL3)-mediated ferroptosis in GC cells. MiR-382-5p was a target of circ_0000190, and circ_0000190 suppressed GC progression partly via serving as miR-382-5p sponge. ZNRF3 was a target of miR-382-5p, and miR-382-5p accelerated the proliferation, motility and restrained the ferroptosis of GC cells partly via regulating ZNRF3. Circ_0000190 overexpression restrained xenograft tumor growth in vivo. Collectively, Circ_0000190 suppressed GC progression via miR-382-5p-dependent regulation of ZNRF3.