Circular RNA hsa_circ_0001658 regulates apoptosis and autophagy in gastric cancer through microRNA-182/Ras-related protein Rab-10 signaling axis

Abstract

ABSTRACT Gastric cancer (GC) is a tumor with high incidence and lack of early diagnostic markers. The aim of this study was to explore novel regulatory circular RNAs (circRNAs) in GC and their underlying mechanisms. Differentially expressed circRNAs were analyzed using the Gene Expression Omnibus (GEO). mRNA and miRNA expression levels were determined using real-time reverse transcription polymerase chain reaction (RT-qPCR). Protein expression was detected using Western blotting. Cellular functions were evaluated using the cell counting kit-8 (CCK-8) assay and flow cytometry analysis. Immunofluorescence analysis was used to visually identify microtubule-associated protein 1 light chain 3 (LC3) puncta on a per-cell basis. Furthermore, dual-luciferase reporter and RNA pull-down assays were performed to verify the interaction between microRNA (miR)-182 and circ_0001658/Ras-related protein Rab-10 (RAB10). Circ_0001658 was identified to be aberrantly expressed in GC tissues and was demonstrated in GC cell lines (AGS and HGC27) in vitro. MiR-182 bound to circ_0001658 and RAB10. Circ_0001658 and RAB10 were upregulated, whereas miR-182 was suppressed in AGS and HGC27 cells. GC cell viability and autophagy were inhibited and apoptosis was promoted after circ_0001658 knockdown, and the cellular functions were reversed by downregulating miR-182. Moreover, upregulated RAB10 neutralized the effects of miR-182 on cell viability, autophagy, and apoptosis of GC cells. Silencing circ_0001658 restrained cell viability, suppressed autophagy, and promoted apoptosis of GC cells by sponging miR-182 to suppress the expression of RAB10. Therefore, circ_0001658 may be a potential therapeutic target for GC.