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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

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Abstract

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.

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Data Availability

Please contact the correspondence author for the data request.

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Authors and Affiliations

  1. Department of Radiological, The Second Hospital of Jilin University, Changchun City, Jilin Province, China

    Yang Liu

  2. Department of Clinical Laboratory, The Second Hospital of Jilin University, No. 218 Ziqiang Street, Changchun, 130001, Jilin Province, China

    Xia Xiao, Yitong Wang & Yanhui Yu

  3. Department of Laboratory, China-Japan Union Hospital of Jilin University, Changchun City, Jilin Province, China

    Jingying Wang

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  1. Yang Liu
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  2. Xia Xiao
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  3. Jingying Wang
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  4. Yitong Wang
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  5. Yanhui Yu
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Contributions

YL was responsible for drafting the manuscript. YL, XX and JW contributed to the analysis and interpretation of data. YL, YW and YY contributed in the data collection. All authors read and approved the final manuscript.

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Correspondence to Yanhui Yu.

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Liu, Y., Xiao, X., Wang, J. et al. Silencing CircEIF3I/miR-526b-5p Axis Epigenetically Targets HGF/c-Met Signal to Hinder the Malignant Growth, Metastasis and Angiogenesis of Hepatocellular Carcinoma. Biochem Genet 61, 48–68 (2023). https://doi.org/10.1007/s10528-022-10239-y

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