Sixth Department of Liver Diseases, Dalian Sixth People Hospital, Dalian Medical University, Dalian, Liaoning, PR China.
Department of Infectious Diseases, The Second Hospital of Dalian Medical University, Dalian Medical University, Dalian, Liaoning, PR China.
Ann Hepatol. 2019 May-Jun;18(3):494-500. doi: 10.1016/j.aohep.2018.11.007. Epub 2019 Apr 18.
Interferon-α (IFN) has shown potential benefits in patients with hepatocellular carcinoma (HCC), and these effects may be mediated by inhibiting cancer cell proliferation. However, the detailed mechanisms underlying the anti-proliferative effects of IFN remain obscure. In this study, we evaluate the role of the novel oncogenic microRNA (miRNA) miR-155 in the anti-proliferative effects of pegylated interferon-α (PEG-IFN) on HCC cells.
The effects of PEG-IFN on HepG2 cell proliferation, migration and invasion were determined using the MTT assay, flow cytometry analysis and the Transwell assay, respectively. Reverse transcription quantitative polymerase chain reaction was used to analyze miR-155 expression. The levels of proteins involved in Wnt/β-catenin signal transduction were determined by western blot analysis and immunofluorescence staining. Mimics of miR-155 were transfected into HepG2 cells to assess the role of miR-155 in the PEG-IFN-induced anti-proliferative effect.
PEG-IFN significantly inhibited the proliferation, migration and invasion of HepG2 cells in a dose-dependent manner by inhibiting cell cycle progression. In parallel with reduced cell proliferation, migration and invasion, miR-155 was efficiently downregulated by PEG-IFN in a dose-dependent manner. Moreover, the transfection of miR-155 decreased the inhibitory effect of PEG-IFN on HepG2cell proliferation, migration and invasion, as well as the downregulation of proteins in the Wnt/β-catenin pathway.
The anti-proliferative effects of PEG-IFN on HCC are at least partially attributable to the downregulation of miR-155.
干扰素-α（IFN）已显示出在肝细胞癌（HCC）患者中的潜在益处，这些效果可能通过抑制癌细胞增殖来介导。然而，IFN 的抗增殖作用的详细机制仍不清楚。在这项研究中，我们评估了新型致癌 microRNA（miRNA）miR-155 在聚乙二醇干扰素-α（PEG-IFN）对 HCC 细胞的抗增殖作用中的作用。
使用 MTT 测定法、流式细胞术分析和 Transwell 测定法分别确定 PEG-IFN 对 HepG2 细胞增殖、迁移和侵袭的影响。逆转录定量聚合酶链反应用于分析 miR-155 的表达。通过 Western blot 分析和免疫荧光染色来确定参与 Wnt/β-catenin 信号转导的蛋白质的水平。将 miR-155 的模拟物转染到 HepG2 细胞中，以评估 miR-155 在 PEG-IFN 诱导的抗增殖作用中的作用。
PEG-IFN 通过抑制细胞周期进程，以剂量依赖性方式显著抑制 HepG2 细胞的增殖、迁移和侵袭。随着细胞增殖、迁移和侵袭的减少，miR-155 也以剂量依赖性方式被 PEG-IFN 有效下调。此外，miR-155 的转染降低了 PEG-IFN 对 HepG2 细胞增殖、迁移和侵袭的抑制作用，以及 Wnt/β-catenin 途径中蛋白质的下调。
PEG-IFN 对 HCC 的抗增殖作用至少部分归因于 miR-155 的下调。
