Implications of microRNA dysregulation in the development of prostate cancer

Abstract

MicroRNAs (miRNAs) are non-coding small RNAs that target mRNA to reduce protein expression. They play fundamental roles in several diseases, including prostate cancer (PCa). A single miRNA can target hundreds of mRNAs and coordinately regulate them, which implicates them in nearly every biological pathway. Hence, miRNAs modulate proliferation, cell cycle, apoptosis, adhesion, migration, invasion and metastasis, most of them constituting crucial hallmarks of cancer. Due to these properties, miRNAs emerged as promising tools for diagnostic, prognosis and management of cancer patients. Moreover, they come out as potential targets for cancer treatment, and several efforts are being made to progress in the field of miRNA-based cancer therapy. In this review, we will summarize the recent information about miRNAs in PCa. We will recapitulate all the miRNAs involved in the androgen pathway and the biology of PCa, focusing in PCa initiation and progression. In particular, we will describe the miRNAs associated with cell proliferation, cell cycle and apoptosis in PCa, as well as invasion, adhesion and metastatic miRNAs. We will revise the recent progress made understanding the role of circulating miRNAs identified in PCa that might be useful for PCa patient stratification. Another key aspect to be discussed in this review is miRNAs' role in PCa therapy, including the miRNAs delivery.Reproduction (2017) 154 R81-R97

The putative tumour suppressor miR-1-3p modulates prostate cancer cell aggressiveness by repressing E2F5 and PFTK1

“…Multiple miRNAs have been observed to be involved in several crucial processes in PCa, such as cell proliferation, apoptosis, invasion and metastasis [9, 12, 14, 15, 17]. The tumor suppression activity of miR-1-3p during tumorigenesis has been well-characterized in several cancers, including colorectal cancer [20], bladder cancer [22] and prostate cancer [18, 19].…”

CLCA2 epigenetic regulation by CTBP1, HDACs, ZEB1, EP300 and miR‐196b‐5p impacts prostate cancer cell adhesion and EMT in metabolic syndrome disease

“…We also described for the first time that CTBP1 modulates multiple miRNAs in PCa from MeS mice that are involved in several pathways related to cancer development and progression. The importance of miRNAs in PCa has already been widely reported; however, there are few reports showing miRNA modulation by CTBP1. Indeed, our group demonstrated that CTBP1 modulates several miRNAs in BrCa, and Chakravarthi et al .…”

Non-coding RNAs: long non-coding RNAs and microRNAs in endocrine-related cancers

“…Changes in miRNA expression in PCa have been reviewed and described below. miRNAs upregulated by AR in PCa include miR-21, miR-27a, miR-32, miR-125b, miR135a, miR-141 and AR overexpression in PCa downregulates miR-99a (Massillo, et al 2017). miR-125b is the most overexpressed miRNA in PCa and downregulates apoptotic genes including BAK1.…”

“…Other oncomiRs overexpressed in PCa are miR-21, miR-32, miR-221, miR-222, miR-181, miR-18a, and miR-429 (reviewed in (Kanwal, et al 2017)). "Andro-miRs": let-7c, miR-31, miR-124, miR-185, miR-205, and miR-488 downregulate AR expression (Massillo et al 2017). Notably, the top four downregulated miRNAs in PCa tissues are miR-187, miR-205, miR-222, and miR-31 (Fuse, et al 2012).…”

“…Additional tumor suppressor miRNAs in PCa and their targets include miR-331-3p that downregulates ERBB2 and AR and is associated with castration-resistant PCa (reviewed in (Kanwal et al 2017)). miRNAs associated with metastasis include downregulation of miR-1, miR-15, miR-16, miR-23a, miR-29b, miR-126, miR-130, miR-132, miR-141, miR-195, miR-200b, miR-200c, miR-203, miR-205, miR-218, miR-375, miR-377, miR-466, miR-573, miR-675, and miR-802 and upregulation of miR-21, miR-22, miR-25, miR-93, miR-106b, miR-154-3p, miR-379, miR-543, and miR-590-3p (reviewed in (Massillo et al 2017)). MiRNAs up-or down-regulated in serum, plasma, and urine with potential prognostic value in separating men with potentially lethal PCa versus indolent disease were recently reviewed (Massillo et al 2017).…”