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Circular RNA hsa_circ_0000519 contributes to angiogenesis and tumor progression in hepatocellular carcinoma through the miR-1296/E2F7 axis

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Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. Uncontrolled angiogenesis plays a critical role in hepatocellular tumor growth and metastasis. In this study, we aimed to investigate the effects of circular RNA hsa_circ_0000519 and the potential involvement of microRNA (miR)-1296 and E2F transcription factor 7 (E2F7) in HCC development. Hsa_circ_0000519 was highly expressed in HCC cells and hepatocellular tumor tissues, and correlated with poor prognosis of HCC patients. Knockdown of hsa_circ_0000519 significantly reduced HCC cell viability, suppressed cell proliferation, and induced cell cycle arrest in G0/G1. Downregulation of hsa_circ_0000519 also inhibited formation of capillary-like endothelial structures in vitro and impeded microvessel formation in mice bearing HCC tumors. The migration and invasive capacities of HCC cells were markedly reduced by hsa_circ_0000519 knockdown. Hsa_circ_0000519 possessed a binding site for microRNA (miR)-1296. Upregulation of hsa_circ_0000519 significantly decreased the miR-1296 expression in both HCC cells and mouse xenografts. Furthermore, E2F7 was a target of miR-1296. Hsa_circ_0000519 positively regulated E2F7 via acting as a miR-1296 sponge. Upregulation of E2F7 abolished the inhibitory effects of hsa_circ_0000519 knockdown on HCC cell proliferation and angiogenesis. In conclusion, hsa_circ_0000519 promoted tumor progression and angiogenesis in HCC through the miR-1296/E2F7 axis. These data suggest the potential clinical application of hsa_circ_0000519 in HCC treatment.

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Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81801990).

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Authors and Affiliations

  1. Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, No. 74 Linjiang Road, Yuzhong District, Chongqing, 400010, China

    Yi Liu, Yaling Zhang, Qian Wang, Shiying Li, Zhiyi Wang & Xiaofeng Shi

  2. Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China

    Hui Tang

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  1. Yi Liu
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Contributions

YL and HT designed the study, supervised the data collection, YZ and QW analyzed the data, interpreted the data, SL, ZW and XS prepared the manuscript for publication and reviewed the draft of the manuscript. All authors have read and approved the manuscript.

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Correspondence to Shiying Li.

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All procedures performed in studies involving human participants were in accordance with the standards upheld by the Ethics Committee of the Second Affiliated Hospital of Chongqing Medical University and with those of the 1964 Helsinki Declaration and its later amendments for ethical research involving human subjects Approval number: 2015 (53). All animal experiments were approved by the Ethics Committee of the Second Affiliated Hospital of Chongqing Medical University for the use of animals and conducted in accordance with the National Institutes of Health Laboratory Animal Care and Use Guidelines Approval number: 2021 (195).

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Liu, Y., Tang, H., Zhang, Y. et al. Circular RNA hsa_circ_0000519 contributes to angiogenesis and tumor progression in hepatocellular carcinoma through the miR-1296/E2F7 axis. Human Cell 36, 738–751 (2023). https://doi.org/10.1007/s13577-022-00854-7

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