REVIEW ARTICLE Microdissecting the role of microRNAs in the pathogenesis of prostate cancer Shiekh Gazalla Ayub a, *, Deepak Kaul a , Taha Ayub b a Department of Experimental Medicine and Biotechnology, Post-Graduate Institute of Medical Sciences and Research, Chandigarh, India; b Department of Social and Preventive Medicine, Government Medical College, Srinagar, Jammu and Kashmir, India MicroRNAs (miRNAs) are naturally occurring, small, non-coding RNA molecules that post- transcriptionally regulate the expression of a large number of genes involved in various biological processes, either through mRNA degradation or through translation inhibition. Since the discov- ery of miRNAs, a vast amount of research has implicated the deregulated expression of miRNAs in different malignancies, including prostate cancer (PCa). Different miRNA expression profiles are reportedly associated with the development, progression, and emergence of castration- resistant PCa (CRPC), suggesting their use in the diagnosis, prognosis, and development of anti-cancer treatment models directed against this disease. However, before their exploitation in terms of therapeutics, a thorough understanding and in-depth mechanistic studies of these miRNAs and the gene networks they orchestrate are necessary for ascertaining their definitive role in the development and progression of PCa. This review attempts to extensively summarize the current knowledge of aberrantly expressed miRNAs and their mode of action in PCa, while highlighting the existing discrepancies and future research warranted. Keywords miRNAs, PCa, androgen-dependent, androgen-independent, hormone-sensitive, castration-resistant ª 2015 Elsevier Inc. All rights reserved. Prostate cancer (PCa) is one of the most common malig- nancies affecting men >40 years old, accounting for approximately 8% of all cancer cases and 15% of cancers in men (1). One of the most troubling aspects of PCa is the inevitable progression of androgen-dependent PCa (ADPC) to an androgen-independent PCa (AIPC) phenotype for which no effective cure has been developed. Although various molecular pathways reportedly help PCa cells survive in an androgen-deficient environment and evolve to androgen-independence, further studies are under way to better understand the key regulatory mechanisms involved in this transition and to gain insight or information relevant to the design of anti-cancer treatment models directed against PCa. To that end, it has become pertinent to test different novel molecules, among which microRNAs (miRNAs) have provided a lucrative option and have recently become an attractive area of research. miRNAs are a class of naturally occurring, small, non- coding subsets of RNAs (18e22 nucleotides) that nega- tively regulate the expression of target genes by binding to the 3 0 untranslated region (UTR) region of messenger RNAs (mRNAs) and inhibiting their translation (2). These interesting molecules have been observed to play an important role in the regulation of several important bio- logical processes, such as development, differentiation, proliferation, cell-cycle regulation, and apoptosis (2e5), demonstrating that aberrant miRNA expression can result in various pathological states, including cancer. The miRNA deregulation plays an important role in cancer and is demonstrated by the fact that 50% of them are traced to chromosomal regions, which are highly prone to deletions, amplifications, or recombinations leading to either their down- or up-regulation (6). The importance of miRNAs in PCa is underscored by various studies that have shown the aberrant expression of different miRNAs in neoplastic PCa tissues compared with normal tissues, providing significant insight into altered cellular features such as growth and the invasive and met- astatic behavior of PCa cells (79) (Figure 1). These differ- entially expressed miRNAs may function in either an Received November 3, 2014; received in revised form February 16, 2015; accepted February 21, 2015. * Corresponding author. E-mail address: gazallakhan@ymail.com 2210-7762/$ - see front matter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.cancergen.2015.02.010 Cancer Genetics - (2015) -