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

Abstract

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. 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. 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. 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.