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miR-143-3p inhibits proliferation and invasion of hepatocellular carcinoma cells by regulating its target gene FGF1

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Abstract

Purpose

To explore FGF1 and miR-143-3p expression in hepatocellular carcinoma (HCC) cells and its related mechanisms.

Methods

Eighty-two HCC patients treated at our hospital from January 2018 to January 2019 were enrolled as Group A, while further 80 healthy people undergoing physical examinations during the same time period were enrolled as Group B. HCC cells and normal human liver cells were purchased, with HepG2 and SMMC-7721 cells transfected with pcDNA3.1-FGF1, si-FGF1, NC, miR-143-3p-inhibitor and miR-143-3p-mimics. FGF1 and miR-143-3p expression was detected by qRT-PCR. The expression of N-cadherin, vimentin, Snail, Slug, E-cadherin and γ-catenin was detected by Western Blotting (WB). Cell proliferation was detected by MTT assay. Cell invasion was detected by Transwell. Cell apoptosis was detected by flow cytometry (FCM).

Results

FGF1 was highly expressed but miR-143-3p was poorly expressed in HCC cells. Areas under the curves (AUCs) of the two indicators were > 0.8. The indicators were correlated with the age, gender, tumor invasion, degree of differentiation, tumor location and TNM staging of the patients. Silencing FGF1 and overexpressing miR-143-3p could promote cell apoptosis, inhibit cell growth, cell epithelial-mesenchymal transition (EMT) and the expression of N-cadherin, vimentin, Snail and Slug, and increase the expression of E-cadherin and γ-catenin. Dual luciferase reporter gene assay (DLRGA) confirmed that FGF1 and miR-143-3p had a targeted relationship. The rescue experiment showed that the proliferation, invasion and apoptosis of HepG2 and SMMC-7721 cells in the miR-143-3p-mimics+pcDNA3.1-FGF1 and miR-143-3p-inhibitor+Si-FGF1 groups were not different from those in the miR-NC group.

Conclusion

Inhibiting FGF1 can upregulate miR-143-3p-mediated Hedgehog signaling pathway, and affect cells’ EMT, proliferation and invasion, so FGF1 is expected to become a potential therapeutic target for HCC.

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Acknowledgements

This study was supported by a grant from the Health Committe of Hubei Province (No. WJ2019M215).

Author information

Authors and Affiliations

  1. Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of China

    J. Peng

  2. Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of China

    J. Peng

  3. Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of China

    J. Peng

  4. Department of Gynecologic Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 117 Zhuodaoquan South Road, Wuhan, 430079, People’s Republic of China

    H. J. Wu, H. F. Zhang, S. Q. Fang & R. Zeng

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Contributions

JP designed the study and drafted the manuscript. HW and HZ were responsible for the collection and analysis of the experimental data. SF and RZ revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript.

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Correspondence to R. Zeng.

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Conflict of interest

The authors declare that they have no conflict of interest.

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The study was approved by Ethical Committee of Hubei Cancer Hospital, and conducted in accordance with the ethical standards.

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Peng, J., Wu, H.J., Zhang, H.F. et al. miR-143-3p inhibits proliferation and invasion of hepatocellular carcinoma cells by regulating its target gene FGF1. Clin Transl Oncol 23, 468–480 (2021). https://doi.org/10.1007/s12094-020-02440-5

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  • DOI: https://doi.org/10.1007/s12094-020-02440-5

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