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image of Upregulation of miR-3130-5p Enhances Hepatocellular Carcinoma Growth by Suppressing Ferredoxin 1: miR-3130-5p Enhances HCC Growth via Inhibiting FDX1
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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 © 2024 The Author(s). Published by Bentham Science Publisher. The Author(s)
This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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2025-03-17
2025-05-02

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Upregulation of miR-3130-5p Enhances Hepatocellular Carcinoma Growth by Suppressing Ferredoxin 1: miR-3130-5p Enhances HCC Growth via Inhibiting FDX1
Bentham Science Publishers , e18761429358008; https://doi.org/10.2174/0118761429358008250305070518
/content/journals/cmp/10.2174/0118761429358008250305070518
/content/journals/cmp/10.2174/0118761429358008250305070518
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  • Article Type:     Research Article
Keywords: miR-3130-5p ; Prognosis ; Ferredoxin 1 ; Therapeutic target ; Biomarker

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