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Abstract
Simple SummaryProstate 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.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.
Highlights
Prostate cancer (PCa) is a major medical issue in men worldwide, and in 2018, there were 1,276,106 estimated new cases in the world
MicroRNA expression profiles vary between tissues and pathological states and miRNAs could potentially serve as biomarkers in PCa [4]
The primary objective of this study is to explore the role of miRNomics in the prostatic tissue environment in men with prostate cancer and to correlate this miRNA expression profile with PCa-related risk factors
Summary
Prostate cancer (PCa) is a major medical issue in men worldwide, and in 2018, there were 1,276,106 estimated new cases in the world. PCa was the most frequently diagnosed cancer among men [1]. MicroRNAs (miRNA, miR) are short, non-coding RNA-molecules that regulate gene expression. They mainly function through partially or completely inhibiting the translation of target mRNAs. MicroRNAs affect many cellular processes, including cell proliferation, differentiation and apoptosis, and play a key role in many syndromes and diseases including cancers [3]. MicroRNA expression profiles vary between tissues and pathological states and miRNAs could potentially serve as biomarkers in PCa [4]. They are generally stable and can be extracted from many kinds of biological samples. MicroRNAs are interesting targets for medical therapies, as modifying their expression levels allows for the modulation of cellular signaling pathways and networks [5]
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