Circular RNA-ABCB10 suppresses hepatocellular carcinoma progression through upregulating NRP1/ABL2 via sponging miR-340-5p/miR-452-5p.

ABSTRACT

OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the most common liver malignancies worldwide with a high rate of recurrence and mortality. Circular RNA-ABCB10 (circ-ABCB10), 724 nucleotides in length, plays a pro-oncogenic role in tumor progression. However, the role of circ-ABCB10 in HCC is still unknown. Therefore, the objective of this study was to determine the role of circ-ABCB10 in HCC progression in vitro and in vivo and to elucidate the underlying mechanism. PATIENTS AND METHODS: Tumor tissues from patients with HCC and multiple HCC cell lines were used for in vitro experiments and a mouse xenograft model was used for in vivo experiments. Quantitative Real Time-PCR, Western blots, lentivirus transfection, cell proliferation assays, cloning formation, migration, and invasion assays, flow cytometry, Luciferase reporter assays, and biotin-coupled probe pull-down assays were performed to investigate the mechanism underlying the effect of circ-ABCB10 on HCC. RESULTS: The results revealed that the expression of circ-ABCB10 was downregulated in both HCC tissues and cell lines and was positively correlated with histological grade and tumor size. The overexpression of circ-ABCB10 exerted inhibitory effects on HCC cell proliferation, invasion, and migration. Mechanistic and functional evidence together showed that circ-ABCB10 elevated expressions of neuropilin-1 (NRP1) and ABL related gene (ABL2) by sponging miR-340-5p and miR-452-5p, which inhibited the progression of HCC. Furthermore, the in vivo study suggests that circ-ABCB10 inhibited tumor growth in nude mice. CONCLUSIONS: In brief, the results demonstrate that circ-ABCB10 exerts anti-tumor roles via miR-340-5p/miR-452-5p-NRP1/ABL2 signaling axis, providing a promising biomarker and therapeutic target for HCC.