Circ_0000190 sponges miR-382-5p to suppress cell proliferation and motility and promote cell death by targeting ZNRF3 in gastric cancer
Man Jiang, Rui Mo, Chang Liu, Haijian Wu
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.