Silencing CircEIF3I/miR-526b-5p Axis Epigenetically Targets HGF/c-Met Signal to Hinder the Malignant Growth, Metastasis and Angiogenesis of Hepatocellular Carcinoma,Biochemical Genetics

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Silencing CircEIF3I/miR-526b-5p Axis Epigenetically Targets HGF/c-Met Signal to Hinder the Malignant Growth, Metastasis and Angiogenesis of Hepatocellular Carcinoma
Biochemical Genetics ( IF 2.1 ) Pub Date : 2022-06-20 , DOI: 10.1007/s10528-022-10239-y
Yang Liu ₁ , Xia Xiao ₂ , Jingying Wang ₃ , Yitong Wang ₂ , Yanhui Yu ₂

Affiliation

Background

Hepatocyte growth factor (HGF)/c-mesenchymal-epithelial transition factor (c-Met) is important for the diagnosis and prognosis of hepatocellular carcinoma (HCC). Circular RNAs (circRNAs) are key regulators of HCC progression, and this study focused on circRNA eukaryotic translation initiation factor 3 subunit I (circEIF3I) with HGF/c-Met in HCC.

Methods

Levels of circEIF3I, microRNA (miR)-526b-5p, HGF, E-cadherin, N-cadherin, and Vimentin were detected by Gene Expression Omnibus database, quantitative PCR and western blotting. Cell functions were measured by detecting cell growth (cell proliferation assay with WST-1 and EdU, colony formation assay, flow cytometry, caspase 3 activity assay, and nude mouse tumorigenicity assay), metastasis (transwell assay and western blotting), angiogenesis (endothelial tube formation assay). Molecular interaction was determined dual-luciferase reporter assay, RNA immunoprecipitation, and Pearson correlation analysis.

Results

Expression of circEIF3I was upregulated in HCC tissues. Knockdown of circEIF3I suppressed cell proliferation epithelial-mesenchymal transition, migration, invasion and tube formation ability but promoted apoptosis of HCC cells. CircEIF3I could sponge miR-526b-5pto regulate downstream HGF. Functionally, circEIF3I regulation in HCC cell progression was associated with miR-526b-5p sponging function and HGF upregulation could attenuate tumor-inhibiting roles of miR-526b-5p. HCC tumor growth was delayed by interfering circEIF3I.

Conclusion

CircEIF3I was an oncogenic circRNA in HCC-, and interfering circEIF3I exhibited anti-HCC activity via circEIF3I-miR-526b-5p-HGF/c-Met pathway.

中文翻译：

沉默 CircEIF3I/miR-526b-5p 轴表观遗传靶向 HGF/c-Met 信号以阻止肝细胞癌的恶性生长、转移和血管生成

背景

肝细胞生长因子 (HGF)/c-间充质-上皮转化因子 (c-Met) 对于肝细胞癌 (HCC) 的诊断和预后具有重要意义。环状 RNA (circRNA) 是 HCC 进展的关键调节因子，本研究重点关注 circRNA 真核翻译起始因子 3 亚基 I (circEIF3I) 与 HGF/c-Met 在 HCC 中的作用。

方法

通过 Gene Expression Omnibus 数据库、定量 PCR 和蛋白质印迹检测 circEIF3I、microRNA (miR)-526b-5p、HGF、E-cadherin、N-cadherin 和 Vimentin 的水平。通过检测细胞生长（使用 WST-1 和 EdU 的细胞增殖测定、集落形成测定、流式细胞术、caspase 3 活性测定和裸鼠致瘤性测定）、转移（transwell 测定和蛋白质印迹）、血管生成（内皮细胞）来测量细胞功能管形成试验）。分子相互作用由双荧光素酶报告基因测定、RNA 免疫沉淀和 Pearson 相关分析确定。

结果

circEIF3I 的表达在 HCC 组织中上调。circEIF3I的敲低抑制了细胞增殖、上皮-间质转化、迁移、侵袭和管形成能力，但促进了HCC细胞的凋亡。CircEIF3I 可以海绵 miR-526b-5p 来调节下游 HGF。在功能上，HCC 细胞进展中的 circEIF3I 调节与 miR-526b-5p 海绵功能相关，并且 HGF 上调可以减弱 miR-526b-5p 的肿瘤抑制作用。干扰 circEIF3I 可延缓 HCC 肿瘤生长。