Abstract
Background
To identify novel miRNAs implicated in prostate cancer metastasis.
Methods
Sixty-five prostate cancer tissues and paired pan-cancer tissues were sequenced. Novel miRNAs were re-analyzed by MIREAP program. Biological functions of miR-N5 were transwell experiment and colony formation. Target genes of miR-N5 were analyzed by bioinformatic analysis. Downstream of target gene was analyzed by The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center (MSKCC) databases and confirmed by CHIP experiment.
Results
We identified a novel miRNA-miR-N5, which was downregulated in PCa cells, PCa tissue, and in the serum of patients with PCa. Knockout of miR-N5 enhanced migration and invasiveness in vitro. miR-N5 specified targeted CREBBP 3′-UTR and inhibited CREBBP expression, which mediated H3K56 acetylation at the promoter of EGFR, β-catenin and CDH1.
Conclusion
This study may shed the light on miR-N5 which influences metastasis via histone acetylation.
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Data availability
All data in this study were available for public.
Abbreviations
- miRNA:
-
MicroRNA
- CREBBP:
-
CREB-binding protein
- H3K56ac:
-
Histone 3 lysine56 acetylation
- PCa:
-
Prostate cancer
- CRPC:
-
Castration-resistant prostate cancer cells
- 3′-UTR:
-
3′-Untranslated Regions
- MSKCC:
-
Memorial Sloan Kettering Cancer Center
- CHIP:
-
Chromatin Immunoprecipitation
- TCGA:
-
The Cancer Genome Atlas
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Funding
This study was funded by the grant of National Natural Science Foundation Youth Project (81702514, C.R.).
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F.B.W. and Z.W. performed the experiments. C.R. and F.B.W. performed assistance for experiment design; Y.Y. performed the data analysis and drafted the manuscript; Z.J.S., M.Y.W., and H.X.W. provided clinical samples. All authors discussed and approved the manuscript; C.R. was responsible for research supervision and coordination.
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The authors declare no conflict of interest.
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All samples were collected from patients with prostate cancer. Leftover samples were sequenced. This study did not change the clinical treatment. All samples were anonymous. The study was approved by the Ethics Committee of Second Medical Military University.
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All patients in the study were from Changhai Hospital, Shanghai, China and informed consent following the principles of Changhai Hospital.
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Wang, F., Zhang, W., Song, Z. et al. A novel miRNA inhibits metastasis of prostate cancer via decreasing CREBBP-mediated histone acetylation. J Cancer Res Clin Oncol 147, 469–480 (2021). https://doi.org/10.1007/s00432-020-03455-9
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DOI: https://doi.org/10.1007/s00432-020-03455-9