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

Binod Kumar, Avi Rosenberg, Su Mi Choi, Karen Fox-Talbot, Angelo Michael Demarzo, Larisa Nonn, William Brennen, Luigi Marchionni, Marc K Halushka, Shawn Lupold

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number7189
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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MicroRNAs
Prostate
Prostatic Neoplasms
Tumor Microenvironment
Epithelium
Neoplasms
Microdissection
Atlases
Prostatectomy
Oncogenes
Cell Culture Techniques
Genome
Gene Expression
Recurrence
Cell Line
Polymerase Chain Reaction

ASJC Scopus subject areas

  • General

Cite this

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title = "Cell-type specific expression of oncogenic and tumor suppressive microRNAs in the human prostate and prostate cancer",
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.",
author = "Binod Kumar and Avi Rosenberg and Choi, {Su Mi} and Karen Fox-Talbot and Demarzo, {Angelo Michael} and Larisa Nonn and William Brennen and Luigi Marchionni and Halushka, {Marc K} and Shawn Lupold",
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T1 - Cell-type specific expression of oncogenic and tumor suppressive microRNAs in the human prostate and prostate cancer

AU - Kumar, Binod

AU - Rosenberg, Avi

AU - Choi, Su Mi

AU - Fox-Talbot, Karen

AU - Demarzo, Angelo Michael

AU - Nonn, Larisa

AU - Brennen, William

AU - Marchionni, Luigi

AU - Halushka, Marc K

AU - Lupold, Shawn

PY - 2018/12/1

Y1 - 2018/12/1

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AB - 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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