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Human Prostate Tissue MicroRNAs and Their Predicted Target Pathways Linked to Prostate Cancer Risk Factors

SIMPLE SUMMARY: Prostate cancer is a major medical issue in men worldwide. In 2018, prostate cancer was the most frequently diagnosed cancer among men in developed countries. MicroRNAs seem to be important regulators of prostate cancer, but better understanding of their role in this disease is still...

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Autores principales: Enwald, Max, Lehtimäki, Terho, Mishra, Pashupati P., Mononen, Nina, Murtola, Teemu J., Raitoharju, Emma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307951/
https://www.ncbi.nlm.nih.gov/pubmed/34298752
http://dx.doi.org/10.3390/cancers13143537
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author Enwald, Max
Lehtimäki, Terho
Mishra, Pashupati P.
Mononen, Nina
Murtola, Teemu J.
Raitoharju, Emma
author_facet Enwald, Max
Lehtimäki, Terho
Mishra, Pashupati P.
Mononen, Nina
Murtola, Teemu J.
Raitoharju, Emma
author_sort Enwald, Max
collection PubMed
description SIMPLE SUMMARY: Prostate cancer is a major medical issue in men worldwide. In 2018, prostate cancer was the most frequently diagnosed cancer among men in developed countries. MicroRNAs seem to be important regulators of prostate cancer, but better understanding of their role in this disease is still needed to develop novel diagnostic tools and treatments. In this study, we aim to achieve insight on the microRNA profile of prostatic tissue environment in men with prostate cancer and to correlate this microRNA expression profile with risk factors of prostate cancer. We also examined the effects of cholesterol-lowering atorvastatin on the prostatic tissue microRNA profile. Our results provide new evidence from the effects of prostate cancer-related factors on the expression of prostate tissue microRNAs. Notably, this can reveal new pathways that may link risk factors to prostate cancer and pinpoint new therapeutic possibilities. ABSTRACT: MicroRNAs are important in prostate cancer development, progression and metastasis. The aim of this study was to test microRNA expression profile in prostate tissue obtained from prostate cancer patients for associations with various prostate cancer related factors and to pinpoint the predicted target pathways for these microRNAs. Prostate tissue samples were obtained at prostatectomy from patients participating in a trial evaluating impact of pre-operative atorvastatin on serum prostate specific antigen (PSA) and Ki-67 expression in prostate tissue. Prostate tissue microRNA expression profiles were analyzed using OpenArray(®) MicroRNA Panel. Pathway enrichment analyses were conducted for predicted target genes of microRNAs that correlated significantly with studied factors. Eight microRNAs correlated significantly with studied factors of patients after Bonferroni multiple testing correction. MiR-485-3p correlated with serum HDL-cholesterol levels. In atorvastatin-treated subjects, miR-34c-5p correlated with a change in serum PSA and miR-138-3p with a change in total cholesterol. In the placebo arm, both miR-576-3p and miR-550-3p correlated with HDL-cholesterol and miR-627 with PSA. In pathway analysis, these eight microRNAs related significantly to several pathways relevant to prostate cancer. This study brings new evidence from the expression of prostate tissue microRNAs and related pathways that may link risk factors to prostate cancer and pinpoint new therapeutic possibilities.
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spelling pubmed-83079512021-07-25 Human Prostate Tissue MicroRNAs and Their Predicted Target Pathways Linked to Prostate Cancer Risk Factors Enwald, Max Lehtimäki, Terho Mishra, Pashupati P. Mononen, Nina Murtola, Teemu J. Raitoharju, Emma Cancers (Basel) Article SIMPLE SUMMARY: Prostate cancer is a major medical issue in men worldwide. In 2018, prostate cancer was the most frequently diagnosed cancer among men in developed countries. MicroRNAs seem to be important regulators of prostate cancer, but better understanding of their role in this disease is still needed to develop novel diagnostic tools and treatments. In this study, we aim to achieve insight on the microRNA profile of prostatic tissue environment in men with prostate cancer and to correlate this microRNA expression profile with risk factors of prostate cancer. We also examined the effects of cholesterol-lowering atorvastatin on the prostatic tissue microRNA profile. Our results provide new evidence from the effects of prostate cancer-related factors on the expression of prostate tissue microRNAs. Notably, this can reveal new pathways that may link risk factors to prostate cancer and pinpoint new therapeutic possibilities. ABSTRACT: MicroRNAs are important in prostate cancer development, progression and metastasis. The aim of this study was to test microRNA expression profile in prostate tissue obtained from prostate cancer patients for associations with various prostate cancer related factors and to pinpoint the predicted target pathways for these microRNAs. Prostate tissue samples were obtained at prostatectomy from patients participating in a trial evaluating impact of pre-operative atorvastatin on serum prostate specific antigen (PSA) and Ki-67 expression in prostate tissue. Prostate tissue microRNA expression profiles were analyzed using OpenArray(®) MicroRNA Panel. Pathway enrichment analyses were conducted for predicted target genes of microRNAs that correlated significantly with studied factors. Eight microRNAs correlated significantly with studied factors of patients after Bonferroni multiple testing correction. MiR-485-3p correlated with serum HDL-cholesterol levels. In atorvastatin-treated subjects, miR-34c-5p correlated with a change in serum PSA and miR-138-3p with a change in total cholesterol. In the placebo arm, both miR-576-3p and miR-550-3p correlated with HDL-cholesterol and miR-627 with PSA. In pathway analysis, these eight microRNAs related significantly to several pathways relevant to prostate cancer. This study brings new evidence from the expression of prostate tissue microRNAs and related pathways that may link risk factors to prostate cancer and pinpoint new therapeutic possibilities. MDPI 2021-07-15 /pmc/articles/PMC8307951/ /pubmed/34298752 http://dx.doi.org/10.3390/cancers13143537 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Enwald, Max
Lehtimäki, Terho
Mishra, Pashupati P.
Mononen, Nina
Murtola, Teemu J.
Raitoharju, Emma
Human Prostate Tissue MicroRNAs and Their Predicted Target Pathways Linked to Prostate Cancer Risk Factors
title Human Prostate Tissue MicroRNAs and Their Predicted Target Pathways Linked to Prostate Cancer Risk Factors
title_full Human Prostate Tissue MicroRNAs and Their Predicted Target Pathways Linked to Prostate Cancer Risk Factors
title_fullStr Human Prostate Tissue MicroRNAs and Their Predicted Target Pathways Linked to Prostate Cancer Risk Factors
title_full_unstemmed Human Prostate Tissue MicroRNAs and Their Predicted Target Pathways Linked to Prostate Cancer Risk Factors
title_short Human Prostate Tissue MicroRNAs and Their Predicted Target Pathways Linked to Prostate Cancer Risk Factors
title_sort human prostate tissue micrornas and their predicted target pathways linked to prostate cancer risk factors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307951/
https://www.ncbi.nlm.nih.gov/pubmed/34298752
http://dx.doi.org/10.3390/cancers13143537
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