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Cell-type specific expression of oncogenic and tumor suppressive microRNAs in the human prostate and prostate cancer

Kumar, Binod, Rosenberg, Avi Z., Choi, Su Mi, Fox-Talbot, Karen, De Marzo, Angelo M., Nonn, Larisa, Brennen, W. Nathaniel, Marchionni, Luigi +2 more·2018·Scientific Reports
DOI 10.1038/s41598-018-25320-zPMC PMC5940660

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Abstract

MiR-1 and miR-143 are frequently reduced in human prostate cancer (PCa), while miR-141 and miR-21 are frequently elevated. Consequently, these miRNAs have been studied as cell-autonomous tumor suppressors and oncogenes. However, the cell-type specificity of these miRNAs is not well defined in prostate tissue. Through two different microdissection techniques, and droplet digital RT-PCR, we quantified these miRNAs in the stroma and epithelium of radical prostatectomy specimens. In contrast to their purported roles as cell-autonomous tumor suppressors, we found miR-1 and miR-143 expression to be predominantly stromal. Conversely, miR-141 was predominantly epithelial. miR-21 was detected in both stroma and epithelium. Strikingly, the levels of miR-1 and miR-143 were significantly reduced in tumor-associated stroma, but not tumor epithelium. Gene expression analyses in human cell lines, tissues, and prostate-derived stromal cultures support the cell-type selective expression of miR-1, miR-141, and miR-143. Analyses of the PCa Genome Atlas (TCGA-PRAD) showed a strong positive correlation between stromal markers and miR-1 and miR-143, and a strong negative correlation between stromal markers and miR-141. In these tumors, loss of miR-1 and gain of miR-21 was highly associated with biochemical recurrence. These data shed new light on stromal and epithelial miRNA expression in the PCa tumor microenvironment.

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  • miR-1 is a known myomiR with skeletal and cardiac muscle expression, and was noted in a colon sample here and was seen in a prostate sample previously.

    “For example, miR-1 (Mir-1-P1), a known myomiR with skeletal and cardiac muscle expression, was noted in a colon sample here and was seen in a prostate sample previously [38, 39].”

    From A curated human cellular microRNAome based on 196 primary cell types (2022) · cites this paper as [38]

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Cited by

Sorted by citations

Authors
Kumar, B., Rosenberg, A. Z., Choi, S. M., Fox-Talbot, K., De Marzo, A. M., Nonn, L., Brennen, W. N., Marchionni, L., Halushka, M. K., & Lupold, S. E.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2018-05-08
Volume
8
Issue
1
ISSN
2045-2322
DOI
10.1038/s41598-018-25320-z
PMC
PMC5940660
Cited by
40
References
1
Language
en
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