Department of Radiology, Binzhou Medical University Hospital, Binzhou, Shandong, P.R. China.
Department of Liver Disease Center, Traditional Chinese Medicine Hospital of Binzhou City, Binzhou, Shandong, P.R. China.
Oncol Res. 2019 Feb 21;27(3):301-309. doi: 10.3727/096504018X15213058045841. Epub 2018 Mar 21.
Our study aimed to investigate the roles and possible regulatory mechanism of miR-1277 in the development of hepatocellular carcinoma (HCC). HCC patients were identified from patients who were diagnosed with focal liver lesions using magnetic resonance imaging (MRI). The expression levels of miR-1277 in the serum of HCC patients and HepG2 cells were measured. Then miR-1277 mimic, miR-1277 inhibitor, or scramble RNA was transfected into HepG2 cells. The effects of miR-1277 overexpression and suppression on HepG2 cell proliferation, migration, and invasion were then investigated. Additionally, the expression levels of epithelial-mesenchymal transition (EMT)-related markers, including E-cadherin, β-catenin, and vimentin, were detected. Target prediction and luciferase reporter assay were performed to explore the potential target of miR-1277. miR-1277 was significantly downregulated in the serum of HCC patients and HepG2 cells. Suppression of miR-1277 promoted HepG2 cell proliferation, migration, and invasion, whereas overexpression of miR-1277 had opposite effects. In addition, after miR-1277 was suppressed, the expressions of E-cadherin and β-catenin were significantly increased, while the expressions of vimentin were markedly decreased. Bone morphogenetic protein 4 (BMP4) was identified as the direct target of miR-1277. Knockdown of BMP4 reversed the effects of miR-1277 suppression on HepG2 cell migration and invasion, as well as the expressions of E-cadherin, β-catenin, and vimentin. Our results indicate that downregulation of miR-1277 may promote the migration and invasion of HepG2 cells by targeting BMP4 to induce EMT. Combination of MRI and miR-1277 level will facilitate the diagnosis and treatment of HCC.
我们的研究旨在探讨 miR-1277 在肝细胞癌（HCC）发展中的作用和可能的调节机制。通过磁共振成像（MRI）诊断为局灶性肝脏病变的患者中确定 HCC 患者。测量 HCC 患者和 HepG2 细胞血清中 miR-1277 的表达水平。然后将 miR-1277 模拟物、miR-1277 抑制剂或 scramble RNA 转染到 HepG2 细胞中。然后研究 miR-1277 过表达和抑制对 HepG2 细胞增殖、迁移和侵袭的影响。此外，检测上皮-间充质转化（EMT）相关标志物的表达水平，包括 E-钙黏蛋白、β-连环蛋白和波形蛋白。进行靶预测和荧光素酶报告基因测定以探索 miR-1277 的潜在靶标。miR-1277 在 HCC 患者和 HepG2 细胞的血清中表达明显下调。抑制 miR-1277 促进 HepG2 细胞增殖、迁移和侵袭，而过表达 miR-1277 则有相反的作用。此外，miR-1277 被抑制后，E-钙黏蛋白和 β-连环蛋白的表达明显增加，而波形蛋白的表达明显减少。骨形态发生蛋白 4（BMP4）被鉴定为 miR-1277 的直接靶标。BMP4 的敲低逆转了 miR-1277 抑制对 HepG2 细胞迁移和侵袭以及 E-钙黏蛋白、β-连环蛋白和波形蛋白表达的影响。我们的结果表明，下调 miR-1277 可能通过靶向 BMP4 诱导 EMT 来促进 HepG2 细胞的迁移和侵袭。将 MRI 与 miR-1277 水平相结合将有助于 HCC 的诊断和治疗。
