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HIPK3 Circular RNA Promotes Metastases of HCC Through Sponging miR-338-3p to Induce ZEB2 Expression

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Abstract

Background

Upregulation of circHIPK3 has been observed in several kinds of malignancies. However, the mechanisms of circHIPK3 in HCC metastases remains unclear. We investigated the role and the mechanisms of circHIPK3 in the development of HCC.

Methods

HCC tissues and paired adjacent non-tumor tissues of surgical patients were used to evaluate circHIPK3 expression. A series of biological experiments had been taken to evaluate the pro-metastatic ability of circHIPK3 during HCC development in vitro and in vivo. The potential mechanisms of circHIPK3 in HCC development were identified by RT-qPCR, Western blot, RIP, and luciferase reporter assays.

Results

CircHIPK3 expression is significantly upregulated during HCC development. Overexpression of circHIPK3 promotes cell migration, invasion, and metastases in vitro and in vivo. CircHIPK3 promoted HCC metastases by sponging miR-338-3p to regulate EMT-associated proteins E-cadherin, vimentin, and ZEB2 expression.

Conclusion

CircHIPK3 plays a regulatory role in metastatic HCC by sponging miR-338-3p to induce ZEB2 expression, thus promoting EMT procession.

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Abbreviations

HCC:

Hepatocellular carcinoma

CircRNAs:

Circular RNAs

EMT:

Epithelial–mesenchymal transition

miRNA:

MicroRNA

CRC:

Colorectal cancer

GC:

Gastric cancer

BC:

Bladder cancer

ISH:

In situ hybridization

RIP:

RNA immunoprecipitation

ZEB2:

Zinc-finger E-box-binding homeobox factor 2

IF:

Immunofluorescence

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Acknowledgments

We thank all the members of our team for their hard work and helpful discussions. Funding was provided by 2017 Key Research & Development Program of Shaanxi Province (Grant No. 2017SF-095).

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Authors and Affiliations

  1. Department of Gastroenterology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

    Weizhi Li, Hui Xue, Yingchao Li, Peijie Li, Fuquan Ma & Mengying Liu

  2. Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong University, No. 157 Xiwu Road, Xi’an, 710004, China

    Shuzhen Kong

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  1. Weizhi Li
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  2. Hui Xue
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  3. Yingchao Li
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Correspondence to Shuzhen Kong.

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Li, W., Xue, H., Li, Y. et al. HIPK3 Circular RNA Promotes Metastases of HCC Through Sponging miR-338-3p to Induce ZEB2 Expression. Dig Dis Sci 66, 3439–3447 (2021). https://doi.org/10.1007/s10620-020-06688-3

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  • DOI: https://doi.org/10.1007/s10620-020-06688-3

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