Department of General Surgery, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Department of Respiration, Xi'an Children Hospital, Xi'an, Shaanxi 710003, P.R. China.
Oncol Rep. 2020 Oct;44(4):1727-1735. doi: 10.3892/or.2020.7702. Epub 2020 Jul 23.
Hepatocellular carcinoma (HCC) is a common hypervascular tumor disease. Endothelial cells, as a crucial component of the tumor microenvironment, have been reported to participate in angiogenesis and influence the development of tumors, including HCC. Recent studies have demonstrated that circulating RNAs (circRNAs) participate in the functional regulation of endothelial cells. However, the expression and function of circRNAs in endothelial cells under the HCC microenvironment is still unclear. In the present study, we analyzed the expression profiles and investigated the role of circRNAs in human umbilical vein endothelial cells (HUVECs) co‑cultured with human primary hepatoma cells. Based on an RNA‑sequencing assay, we screened 19 significantly downregulated circRNAs in HUVECs under an HCC microenvironment. Subsequently, we validated the expression of the candidate circRNAs using RT‑qPCR, and selected two of the most downregulated circRNAs among them, circ_4911 and circ_4302. Next, through circRNA overexpression experiments, we demonstrated that overexpression of circ_4911 and circ_4302 both inhibited the proliferation and migration of HUVECs, and arrested cells at the GO/G1 stage, while promoting adhesion. Overall, in the present study, we identified the roles of circ_4911 and circ_4302 in regulating functions of HUVECs under an HCC microenvironment.
肝细胞癌（HCC）是一种常见的富血管肿瘤疾病。内皮细胞作为肿瘤微环境的重要组成部分，据报道参与血管生成，并影响肿瘤的发展，包括 HCC。最近的研究表明，循环 RNA（circRNA）参与内皮细胞的功能调节。然而，HCC 微环境下内皮细胞中 circRNA 的表达和功能尚不清楚。在本研究中，我们分析了 RNA 测序分析筛选出的在人脐静脉内皮细胞（HUVEC）与人原发性肝癌细胞共培养的 HCC 微环境下显著下调的 19 个 circRNA 的表达谱，并研究了它们的作用。随后，我们使用 RT-qPCR 验证了候选 circRNA 的表达，并从中选择了两个下调最明显的 circRNA，circ_4911 和 circ_4302。接下来，通过 circRNA 过表达实验，我们证明了 circ_4911 和 circ_4302 的过表达均抑制了 HUVEC 的增殖和迁移，并将细胞阻滞在 GO/G1 期，同时促进了细胞黏附。总之，在本研究中，我们鉴定了 circ_4911 和 circ_4302 在调节 HCC 微环境下 HUVEC 功能中的作用。
