Abstract

Background Circular RNA RNA-binding motif protein 23 (circ_RBM23; ID: hsa_circ_0000524) is a novel regulator in hepatocellular carcinoma (HCC). Herein, we planned to investigate its role in sorafenib resistance in HCC. Method Levels of circ_RBM23, microRNA (miR)−338–3p, Ras-related GTPase-trafficking protein (RAB1B), Snail and E-cadherin were detected by real-time quantitative PCR and western blotting . Sorafenib resistant (SR) HCC cells (Huh7/SR and SK-HEP-1/SR) were established by acquisition of sorafenib resistance, and cell functions were measured by MTT assay , Edu assay, colony formation assay, apoptosis assay , transwell assay, and in vivo xenograft formation assay. Crosslink between miR-338–3p and circ_RBM23 or RAB1B was confirmed by bioinformatics analysis and dual-luciferase reporter assay. Results Circ_RBM23 upregulation was discovered in the tissues of SR patients and SR cells, which was accompanied with miR-338–3p downregulation and RAB1B upregulation. The 50% inhibitory concentration (IC 50 ) of sorafenib in SR cells was greatly suppressed by interfering circ_RBM23 or reinforcing miR-338–3p, allied with this was the inhibition of EdU-positive cell rate, colony formation and migration/invasion abilities under sorafenib treatment , as well as the enhancement of apoptotic rate . Moreover, circ_RBM23 inhibition delayed tumor growth of Huh7/SR cells under sorfanib treatment in vivo . Conclusion Circ_RBM23 promoted chemoresistance, malignant proliferation, migration and invasion of SR HCC cells by modulating miR-338–3p/RAB1B axis.