Department of Hepatobiliary Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, PR China.
Department of Hepatobiliary Surgery of the Eastern Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China.
Gene. 2019 Jan 30;683:253-261. doi: 10.1016/j.gene.2018.10.043. Epub 2018 Oct 17.
Circular RNAs (circRNAs) as new types of endogenous non-coding RNAs have been recently identified important roles in certain types of pathological responses, and in the occurrence and progression of a variety of human malignancies. In the present study, we aimed to evaluate the role of has_circ_0078710, which is back spliced by THBS2 gene in hepatocellular carcinoma (HCC). Expression levels of has_circ_0078710 were tested in both HCC tissue samples and cells using real-time qRT-PCR. Has_circ_0078710 was significantly unregulated in HCC tissues and cells. Moreover, HCC patients with high level of has_circ_0078710 had the advance stage (TNM III-IV). Finally, we constructed an interaction network among circRNA-miRNA-mRNA and we identified miR-31 as the has_circ_0078710-associatedmiRNA. Furthermore, overexpression of has_circ_0078710 in HCC could up-regulate HDAC and CDK2 levels by sponging miR-31, simultaneously mediating the expression of cell cycle components (cyclin A, cyclin D1, CDK4) and negative cell cycle regulator p21. In vitro and in vivo functional studies showed that overexpression of has_circ_0078710 in HepG2, SMMC-7721 cell lines significantly promoted cell proliferation, migration, invasion and tumor growth by inducing the cell cycle progression. In summary, we identified Has_circ_0078710 as a potential HCC biomarker.
环状 RNA（circRNAs）作为新型内源性非编码 RNA，最近被鉴定在某些类型的病理反应中具有重要作用，并在多种人类恶性肿瘤的发生和进展中发挥作用。在本研究中，我们旨在评估由 THBS2 基因剪接的环状 RNA（circRNA）has_circ_0078710 在肝细胞癌（HCC）中的作用。采用实时 qRT-PCR 检测 HCC 组织样本和细胞中 has_circ_0078710 的表达水平。在 HCC 组织和细胞中，has_circ_0078710 的表达水平显著上调。此外，高水平 has_circ_0078710 的 HCC 患者具有晚期（TNM III-IV）。最后，我们构建了 circRNA-miRNA-mRNA 的相互作用网络，鉴定出 miR-31 是 has_circ_0078710 的相关 miRNA。此外，has_circ_0078710 在 HCC 中的过表达通过海绵吸附 miR-31 上调 HDAC 和 CDK2 水平，同时调节细胞周期成分（cyclin A、cyclin D1、CDK4）和负细胞周期调节剂 p21 的表达。体外和体内功能研究表明，过表达 has_circ_0078710 可显著促进 HepG2、SMMC-7721 细胞系的细胞增殖、迁移、侵袭和肿瘤生长，从而诱导细胞周期进程。总之，我们确定 Has_circ_0078710 是一种潜在的 HCC 生物标志物。
