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MiRNA in Prostate Cancer: New Prospects for Old Challenges.

ABSTRACT: Prostate cancer (PCa) is one of the most commonly diagnosed cancers among men but has limited prognostic biomarkers available for follow up. MicroRNAs (miRNAs) are small non-coding RNAs that regulate expression of their target genes. Accumulating experimental evidence reports differential miRNA expression in PCa, and that miRNAs are actively involved in the pathogenesis and progression of PCa. miRNA and androgen receptor signaling cross-talk is an established factor in PCa pathogenesis. Differential miRNA expression was found between patients with high versus low Gleason scores, and was also observed in patients with biochemical failure, hormone-resistant cancer and in metastasis. Metastasis requires epithelial-mesenchymal transition which shares many cancer stem cell biological characteristics and both are associated with miRNA dysregulation. In the era of personalized medicine, there is a broad spectrum of potential clinical applications of miRNAs. These applications can significantly improve PCa management including their use as diagnostic and/or prognostic markers, or as predictive markers for treatment efficiency. Preliminary evidence demonstrates that miRNAs can also be used for risk stratification. Circulatory miRNAs can serve as non-invasive biomarkers in urine and/or serum of PCa patients. More recently, analysis of miRNAs and circulating tumor cells are gaining significant attention. Moreover, miRNAs represent an attractive new class of therapeutic targets for PCa. Here, we summarize the current knowledge and the future prospects of miRNAs in PCa, their advantages, and potential challenges as tissue and circulating biomarkers. Prostate cancer (PCa) is the most commonly diagnosed cancer among men in western populations. The American Cancer Society estimated 239, 590 new cases and 29, 720 expected deaths in the USA in 2013. One in every six men are at risk of developing PCa during their lifetime (1). Currently, the standard biomarker for PCa diagnosis is prostate-specific antigen (PSA), which has its limitations, leading to the risks of PCa over diagnosis and harmful overtreatment. The prognostic value of PSA is also questionable (2). Stepping into the new epoch of personalized medicine, molecular markers are urgently needed to improve the different aspects of PCa management (3). miRNAs represent an attractive class of emerging biomarkers that can help in this regard (4;5).

SUBMITTER: Mekhail SM

PROVIDER: S-EPMC4975192 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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miRNA in Prostate Cancer: New Prospects for Old Challenges.

Mekhail Samy M SM Yousef Peter G PG Jackinsky Stephen W SW Pasic Maria M Yousef George M GM

EJIFCC 20140428 1

Prostate cancer (PCa) is one of the most commonly diagnosed cancers among men but has limited prognostic biomarkers available for follow up. MicroRNAs (miRNAs) are small non-coding RNAs that regulate expression of their target genes. Accumulating experimental evidence reports differential miRNA expression in PCa, and that miRNAs are actively involved in the pathogenesis and progression of PCa. miRNA and androgen receptor signaling cross-talk is an established factor in PCa pathogenesis. Differen ...[more]

PMID: 27683458

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Project description:Prostate cancer is the second most common male cancer worldwide showing the highest rates of incidence in Western Europe. Although the measurement of serum prostate-specific antigen levels is the current gold standard in PCa diagnosis, PSA-based screening is not considered a reliable diagnosis and prognosis tool due to its lower sensitivity and poor predictive score which lead to a 22%-43% overdiagnosis, unnecessary biopsies, and over-treatment. These major limitations along with the heterogeneous nature of the disease have made PCa a very unappreciative subject for diagnostics, resulting in poor patient management; thus, it urges to identify and validate new reliable PCa biomarkers that can provide accurate information in regard to disease diagnosis and prognosis. Researchers have explored the analysis of microRNAs (miRNAs), messenger RNAs (mRNAs), small proteins, genomic rearrangements, and gene expression in body fluids and non-solid tissues in search of lesser invasive yet efficient PCa biomarkers. Although the presence of miRNAs in body fluids like blood, urine, and saliva initially sparked great interest among the scientific community; their potential use as liquid biopsy biomarkers in PCa is still at a very nascent stage with respect to other well-established diagnostics and prognosis tools. Up to date, numerous studies have been conducted in search of PCa miRNA-based biomarkers in whole blood or blood serum; however, only a few studies have investigated their presence in urine samples of which less than two tens involve the detection of miRNAs in extracellular vesicles isolated from urine. In addition, there exists some discrepancy around the identification of miRNAs in PCa urine samples due to the diversity of the urine fractions that can be targeted for analysis such as urine circulating cells, cell-free fractions, and exosomes. In this review, we aim to discuss research output from the most recent studies involving the analysis of urinary EVs for the identification of miRNA-based PCa-specific biomarkers.

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MiRNA in Prostate Cancer: New Prospects for Old Challenges.

Publications

miRNA in Prostate Cancer: New Prospects for Old Challenges.

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