1 Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University , Zhengzhou, China .
2 Department of Gastroenterology, Luoyang Central Hospital Affiliated to Zhengzhou University , Luoyang, China .
Cancer Biother Radiopharm. 2018 Jun;33(5):194-202. doi: 10.1089/cbr.2017.2424.
Primary hepatocellular carcinoma (HCC) is one of the most common malignant tumors. At present, the molecular mechanism of HCC remains unclear. A recent circular RNA (circRNA) profiling study showed that circRBM23 expression was upregulated in HCC tissues. Therefore, in this study, the impact of circRBM23 during the progression of HCC was evaluated. The expression levels of circRBM23 and miR-138 in HCC tissues and HCC cell lines were determined by RT-PCR and the results indicated that circRBM23 expression was increased in the HCC tissues and HCC cell lines, whereas miR-138 expression was decreased. An upregulation of circRBM23 expression in HCC cells was shown to increase cell viability, and also increased the ability of cells to migrate. Downregulation of circRBM23 was found to decrease cell viability, proliferation, and migration, and promote the expression of miR-138 and its related target genes, vimentin, and CCND3. Moreover, miR-138 was found to regulate HCC cell viability and migration, and the levels of vimentin and CCND3 protein expression were found to be inversely correlated with those of miR-138 expression. The downregulation of circRBM23 in HCC tissues can regulate the miR-138-mediated signal pathway by promoting miR-138 expression. The results in vivo demonstrated that circRBM23 is required for the tumorigenesis with downregulation of tumor suppressor miR-138. These data indicated that upregulated circRBM23 functioned as oncogene in HCC through regulating the tumor suppressor miR-138.
原发性肝细胞癌（HCC）是最常见的恶性肿瘤之一。目前，HCC 的分子机制尚不清楚。最近的环状 RNA（circRNA）谱分析研究表明，circRBM23 在 HCC 组织中表达上调。因此，在本研究中，评估了 circRBM23 在 HCC 进展过程中的影响。通过 RT-PCR 测定 HCC 组织和 HCC 细胞系中 circRBM23 和 miR-138 的表达水平，结果表明 circRBM23 在 HCC 组织和 HCC 细胞系中表达增加，而 miR-138 表达降低。上调 HCC 细胞中的 circRBM23 表达可增加细胞活力，并增强细胞迁移能力。下调 circRBM23 发现可降低细胞活力、增殖和迁移，并促进 miR-138 及其相关靶基因 vimentin 和 CCND3 的表达。此外，发现 miR-138 可调节 HCC 细胞活力和迁移，并且 vimentin 和 CCND3 蛋白表达水平与 miR-138 表达水平呈负相关。在 HCC 组织中下调 circRBM23 可通过促进 miR-138 表达来调节 miR-138 介导的信号通路。体内结果表明，下调肿瘤抑制因子 miR-138 可促进 circRBM23 下调 HCC 肿瘤发生。这些数据表明，上调的 circRBM23 通过调节肿瘤抑制因子 miR-138 在 HCC 中发挥癌基因作用。
