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miR-9-5p expression is associated with vascular invasion and prognosis in hepatocellular carcinoma, and in vitro verification

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Abstract

Purpose

Hepatocellular carcinoma (HCC) is a common liver malignancy. Early vascular invasion (VI) has been associated with poor prognosis in HCC patients. MicroRNAs (miRNAs) play a significant role in the emergence and development of many tumor types.

Methods

Differential expression analysis of miRNAs related to VI was performed based on data from the TCGA database, and survival-associated miRNAs identified. We identified miR-9-5p as a survival-related miRNA and verified its expression in 61 clinical samples using quantitative real-time PCR. We further performed functional enrichment analysis, protein-protein interaction analysis, univariate and multivariate analysis of the survival-related miRNAs, and cell function assays.

Results

In this study, we identified miR-9-5p that could predict VI and prognosis in HCC patients. Cellular experiments demonstrated that downregulation of miR‑9‑5p inhibits migration, invasion, and angiogenesis of HCC cells. Further, we explored and verified the possible mechanism through which miR-9-5p is involved in HCC progression. Univariate and multivariate analysis revealed that miR-9-5p was an independent risk factor for HCC. Finally, the nomogram based on miR-9-5p showed a good predictive value of HCC survival.

Conclusions

MiR-9-5p is associated with VI in HCC, and higher expression of miR-9-5p indicates poor prognosis in HCC.

Graphical abstract

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Data availability

The Online data are available at the TCGA database (https://portal.gdc.cancer.gov/). The clinical patient data used during this study can be obtained from the corresponding author upon reasonable request.

Code availability

Not applicable.

Abbreviations

HCC:

Hepatocellular carcinoma

VI:

Vascular invasion

miRNAs:

MicroRNAs

mRNAs:

Messenger RNAs

TCGA:

The Cancer Genome Atlas

DEMs:

Differentially expressed miRNAs

RT-qPCR:

Quantitative real‑time PCR

FBS:

Fetal bovine serum

GO:

Gene Ontology

KEGG:

Kyoto Encyclopedia of Genes and Genomes

PPI:

Protein–protein interaction

OS:

Overall survival

ROC:

Receiver operator characteristic

AUC:

Area under curve

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Acknowledgements

The authors thank all the workers who participated in the construction of TCGA database and the patients who donated samples. The authors thank the Department of Biobank, Subei People’s Hospital of Jiangsu province for collecting, storing, and classifying patient specimens used in this study.

Funding

This work was supported by The National Natural Science Foundation of China under Grant number 81871909; “13th five-year Plan” Science and Education strong Health Project leading personnel of Yangzhou under Grant number YZCXTD201801; and Provincial-level discipline leader of the NJPH under Grant number DTRC201809.

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Author notes

  1. Yuan Chen and Hao Xu have contributed equally to this work.

Authors and Affiliations

  1. Yangzhou University Medical College, Yangzhou, Jiangsu, China

    Yuan Chen, Hao Xu & Hao Tang

  2. Dalian Medical University, Dalian, Liaoning, China

    Hongyuan Li

  3. Department of Hepatobiliary and Pancreatic Surgery, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China

    Chi Zhang, Shengjie Jin & Dousheng Bai

  4. General Surgery Department of Siyang Hospital, Suqian, Jiangsu, China

    Hao Xu

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  1. Yuan Chen
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Contributions

YC conceived and designed the experiment, collected experimental data, wrote the manuscript draft, and finally approved the manuscript. HX collected and analyzed the experimental data and reviewed the manuscript. HT and HL assisted in the experiments and collected patient data. CZ and SJ reviewed the manuscript. DB reviewed the manuscript and provided financial support.

Corresponding author

Correspondence to Dousheng Bai.

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Conflict of interest

All authors declare no conflicts of interest.

Ethical approval and consent to participate

The study complied with the principles set forth in the Declaration of Helsinki. The data obtained from the TCGA database are all open access data, which conforms to the database usage specification. Written informed consent was obtained from all participants prior to the study, and this study was approved by the Ethics Committee of the Northern Jiangsu People’s Hospital (approval number: 2020ky-067).

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Chen, Y., Xu, H., Tang, H. et al. miR-9-5p expression is associated with vascular invasion and prognosis in hepatocellular carcinoma, and in vitro verification. J Cancer Res Clin Oncol 149, 14657–14671 (2023). https://doi.org/10.1007/s00432-023-05257-1

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  • DOI: https://doi.org/10.1007/s00432-023-05257-1

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