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2000
Volume 17, Issue 1
  • ISSN: 1874-4672
  • E-ISSN: 1874-4702
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Abstract

Background

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, necessitating the exploration of novel therapeutic targets. Although accumulating studies have identified Ferredoxin 1 (FDX1), a key regulator of cuproptosis, as a candidate tumor suppressor and potential therapeutic target, its role and mechanism remain elusive in HCC.

Methods

The FDX1 expression was investigated in human HCC tissues and cell lines. Potential microRNAs targeting FDX1 were predicted by bioinformatic analysis and validated using qPCR screening, a dual luciferase reporter assay, MiR-3130-5p and miR-1910-3p mimics and inhibitors, overexpression plasmids, and xenograft nude mouse model. The correlation between miR-3130-5p/FDX1 axis and HCC patient prognosis was analyzed by using Kaplan-Meier survival analysis.

Results

We demonstrated that the expression of FDX1 was downregulated in human HCC tissues and cell lines compared to non-cancerous counterparts, and the downregulation of FDX1 was associated with poor overall survival in HCC patients. Subsequent bioinformatic analysis and experimental validations showed that FDX1 expression was reduced by microRNA (miR)-3130-5p mimic while induced by miR-3130-5p inhibitor. Further, miR-3130-5p was upregulated in HCC tissues and cells, correlating with a poor prognosis of HCC patients. Besides, lentivirus-mediated overexpression of miR-3130-5p significantly enhanced HCC growth in xenograft nude mouse models. Mechanistically, it was demonstrated that miR-3130-5p inhibited FDX1 expression binding to its 3' untranslated region (3' UTR), while overexpression of FDX1 counteracted the promoting effect of miR-3130-5p on HCC cell proliferation.

Conclusion

These findings suggest the miR-3130-5p/FDX1 axis as a prognostic biomarker as well as a potential therapeutic target in HCC.

© 2024 The Author(s).
© 2024 The Author(s). Published by Bentham Science Publishers. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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Upregulation of miR-3130-5p Enhances Hepatocellular Carcinoma Growth by Suppressing Ferredoxin 1
Curr Mol Pharmacol 17, E18761429358008 (2024); https://doi.org/10.2174/0118761429358008250305070518
/content/journals/cmp/10.2174/0118761429358008250305070518
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  • Article Type:     Research Article
Keyword(s): Biomarker; Ferredoxin 1; Hepatocellular carcinoma; miR-3130-5p; Prognosis; Therapeutic target

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