Abstract

Prostate cancer (PCa) is currently the most frequently diagnosed malignancy in the western countries. It is more prevalent in older men with 75% of the incident cases above 65 years old. After radical prostatectomy, approximately 30% of men develop clinical recurrence with elevated serum prostate-specific antigen levels. Therefore, it is important to unravel the molecular mechanisms underlying PCa progression to develop novel diagnostic/therapeutic approaches. In this study, it is aimed to compare the microRNA (miRNA) profile of recurrent and non-recurrent prostate tumor tissues to explore the possible involvement of miRNAs in PCa progression. Total RNA from 41 recurrent and 41 non-recurrent PCa tissue samples were used to investigate the miRNA signature in PCa specimens. First of all, 20 recurrent and 20 non-recurrent PCa samples were profiled using miRNA microarray chips. Of the differentially expressed miRNAs, miR-1, miR-133b and miR-145* were selected for further validation with qRT-PCR in a different set of 21 recurrent and 21 non-recurrent PCa samples. Data were statistically analyzed using two-sided Student's t-test, Pearson Correlation test, Receiver operating characteristic analysis. Our results demonstrated that miR-1 and mir-133b have been significantly downregulated in recurrent PCa specimens in comparison to non-recurrent PCa samples and have sufficient power to distinguish recurrent specimens from non-recurrent ones on their own. Here, we report that the relative expression of miR-1 and mir-133b have been significantly reduced in recurrent PCa specimens in comparison to non-recurrent PCa samples, which can serve as novel biomarkers for prediction of PCa progression.

Highlights

  • Prostate cancer (PCa) is currently the most frequently diagnosed malignancy and the second leading cause of cancer deaths among men over the age of 50 years in the western countries [1]

  • Patients RNAs were isolated from 41 recurrent and 41 non-recurrent cancers from radical prostatectomies, which contained at least 70% tumor tissue, which were obtained from Baylor College of Medicine Prostate Cancer program

  • The average age at the time of surgery of the PCa patients with recurrence were 62.866, whereas those without recurrence had an average age of 61.767.2

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Summary

Introduction

Prostate cancer (PCa) is currently the most frequently diagnosed malignancy and the second leading cause of cancer deaths among men over the age of 50 years in the western countries [1]. MicroRNAs (miRNA) are endogenously synthesized, regulatory non-coding small RNAs comprised of around 20 nucleotides and considered as a novel class of gene regulators. About half of the annotated human miRNAs are located in fragile sites of the genome suggesting that these small molecules might have a vital function in pathogenesis of several diseases including cancer [8,9]. They have been shown to be able to distinguish differentiation states of several malignancies including breast, lung and colon cancers. There are, a limited number of reports in the literature studied miRNAs in prostate cancer progression

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