Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Pathology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China.
J Cell Physiol. 2019 Aug;234(10):17775-17785. doi: 10.1002/jcp.28403. Epub 2019 Mar 12.
Circular RNAs have been found to be aberrantly expressed in tumors and their significance in tumorigenesis has been focused on. The role of circDYNC1H1 in hepatocellular carcinoma (HCC) pathogenesis and its relationship with miR-140-5p were explored. The expression of circDYNC1H1, miR-140-5p, and SULT2B1 in HCC tissues and cells was measured, and Pearson's analysis was used to analyze their expression correlation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assays were performed to determine cell proliferation and migration. Binding between circDYNC1H1 and miR-140-5p was evaluated with RNA pull-down assay. A luciferase reporter assay was conducted to assess the interaction between circDYNC1H1 and miR-140-5p and between miR-140-5p and SULT2B1. circDYNC1H1 was highly expressed in HCC tissues (n = 20), and it was negatively associated with the expression of miR-140-5p but positively correlated with SULT2B1 messenger RNA expression. circDYNC1H1 was upregulated in cell lines of HCC. Interference of circDYNC1H1 suppressed cell proliferation and migration of HCC. circDYNC1H1 acted as a sponge of miR-140-5p. miR-140-5p controlled SULT2B1 expression by targeting its 3'-untranslated region. circDYNC1H1 enhanced SULT2B1 expression via sponging miR-140-5p. Downregulation of circDYNC1H1 disturbed cell proliferation and migration of HCC through miR-140-5p/SULT2B1 pathway. Silencing of circDYNC1H1 delayed tumor growth in HCC mouse model. Acting like a sponge of miR-140-5p, silenced circDYNC1H1 downregulated SULT2B1 to restrain HCC cell proliferation and migration, which is adverse to HCC growth and progression.
环状 RNA 已被发现在肿瘤中异常表达，其在肿瘤发生中的作用受到关注。本研究旨在探讨环状 RNA 动力蛋白 1 同源物 1（circDYNC1H1）在肝细胞癌（HCC）发病机制中的作用及其与 miR-140-5p 的关系。检测 HCC 组织和细胞中 circDYNC1H1、miR-140-5p 和 SULT2B1 的表达，采用 Pearson 分析其表达相关性。采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）比色法和 Transwell 实验检测细胞增殖和迁移。采用 RNA 下拉实验评估 circDYNC1H1 与 miR-140-5p 的结合。采用荧光素酶报告基因实验评估 circDYNC1H1 与 miR-140-5p 以及 miR-140-5p 与 SULT2B1 之间的相互作用。circDYNC1H1 在 HCC 组织（n=20）中高表达，与 miR-140-5p 的表达呈负相关，但与 SULT2B1 信使 RNA 表达呈正相关。circDYNC1H1 在 HCC 细胞系中上调。circDYNC1H1 干扰抑制 HCC 细胞的增殖和迁移。circDYNC1H1 作为 miR-140-5p 的海绵。miR-140-5p 通过靶向其 3'-非翻译区来控制 SULT2B1 的表达。circDYNC1H1 通过海绵 miR-140-5p 增强 SULT2B1 的表达。下调 circDYNC1H1 通过 miR-140-5p/SULT2B1 通路干扰 HCC 细胞的增殖和迁移。沉默 circDYNC1H1 可延迟 HCC 小鼠模型中的肿瘤生长。作为 miR-140-5p 的海绵，沉默的 circDYNC1H1 下调 SULT2B1，抑制 HCC 细胞的增殖和迁移，不利于 HCC 的生长和进展。
