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miR-19a and miR-421 target PCA3 long non-coding RNA and restore PRUNE2 tumor suppressor activity in prostate cancer

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Abstract

Background

Prostate cancer antigen 3 (PCA3) is the most promising diagnostic biomarker for the differential diagnosis of prostate cancer identified to date. As a dominant-negative oncogene, PCA3 negatively regulates the expression of tumor suppressor PRUNE2 (a human homolog of the Drosophila prune gene) gene. Although interaction between PCA3-PRUNE2 was clearly reported, the precise mechanism how PCA3 is upregulated in prostate cancer remained highly elusive. Accordingly, here we aimed demonstrate the role of microRNAs in PCA3 upregulation and interplay between these miRNAs and PCA3-PRUNE2 axis.

Methods and results

We evaluated expression of PCA3, PRUNE2 and miRNAs by quantitative reverse transcription polymerase chain reaction. Overexpression and silencing of miRNAs were achieved by synthetic miRNA mimics and inhibitors, respectively. Colony formation, migration, apoptosis, and cell cycle assays were performed to reveal the effects of miRNA modulation. We identified that PCA3 expression was significantly downregulated in both prostate cancer tissues and cells and inversely correlated with the expressions of miR-19a and miR-421. Restoring the functions of miR-19a and miR-421 by miRNA mimics significantly downregulated the expression of PCA3 and promoted apoptosis and cell cycle blockade and interfered with the proliferation and migration in prostate cancer cells. Conversely, silencing the expressions of these miRNAs yielded the opposite effect.

Conclusions

Collectively, our results uncover a previously unrecognized novel mechanism on PCA3 upregulation in prostate cancer and proved that miR-19a and miR-421 might be responsible for the increased expression of PCA3, indicating that both miRNAs might be novel candidates for prostate cancer diagnosis and therapy.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Code availability

Not applicable.

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Acknowledgements

This study complies with the publication guidelines of TCGA, and the results presented here are in part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga.

Funding

The present study was supported by the Grant from the Adiyaman University (Grand Number: SHMYOMAP/2020–0001).

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Authors and Affiliations

  1. Department of Medical Services and Techniques, Vocational School of Health Services, Adiyaman University, Adiyaman, Turkey

    Esra Bozgeyik

  2. Department of Physiology, Faculty of Medicine, Adiyaman University, Adiyaman, Turkey

    Sayad Kocahan

  3. Program of Medical Promotion and Marketing, Vocational School of Health Services, Harran University, Şanlıurfa, Turkey

    Ebru Temiz

  4. Department of Medical Genetics, Faculty of Medicine, Adiyaman University, Adiyaman, Turkey

    Haydar Bagis

Authors
  1. Esra Bozgeyik
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  2. Sayad Kocahan
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  3. Ebru Temiz
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  4. Haydar Bagis
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Contributions

EB: Conceptualization, Methodology, Data curation, Writing—original draft, Writing—review & editing SK: Conceptualization, Methodology, Writing—review & editing ET: Methodology, Writing—review & editing HB: Methodology, Writing—review & editing.

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Correspondence to Esra Bozgeyik.

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Bozgeyik, E., Kocahan, S., Temiz, E. et al. miR-19a and miR-421 target PCA3 long non-coding RNA and restore PRUNE2 tumor suppressor activity in prostate cancer. Mol Biol Rep 49, 6803–6815 (2022). https://doi.org/10.1007/s11033-021-06996-5

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  • DOI: https://doi.org/10.1007/s11033-021-06996-5

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