miRNAs as Therapeutic Tools and Biomarkers for Prostate Cancer

Abstract

Prostate cancer (PCa) is the fifth cause of tumor-related deaths in man worldwide. Despite the considerable improvement in the clinical management of PCa, several limitations emerged both in the screening for early diagnosis and in the medical treatment. The use of prostate-specific antigen (PSA)-based screening resulted in patients’ overtreatment and the standard therapy of patients suffering from locally advanced/metastatic tumors (e.g., radical prostatectomy, radiotherapy, and androgen deprivation therapy) showed time-limited efficacy with patients undergoing progression toward the lethal metastatic castration-resistant PCa (mCRPC). Although valuable alternative therapeutic options have been recently proposed (e.g., docetaxel, cabazitaxel, abiraterone, enzalutamide, and sipuleucel-T), mCRPC remains incurable. Based on this background, there is an urgent need to identify new and more accurate prostate-specific biomarkers for PCa diagnosis and prognosis and to develop innovative medical approaches to counteract mCRPC. In this context, microRNA (miRNAs) emerged as potential biomarkers in prostate tissues and biological fluids and appeared to be promising therapeutic targets/tools for cancer therapy. Here we overview the recent literature and summarize the achievements of using miRNAs as biomarkers and therapeutic targets/tools for fighting PCa.

Up-Regulation of LINC00665 Facilitates the Malignant Progression of Prostate Cancer by Epigenetically Silencing KLF2 Through EZH2 and LSD1

“…LncRNA, a type of ncRNA with a transcript longer than 200 nt, does not encode proteins or only encodes short peptides (14,15) A large number of studies have revealed that lncRNA plays a non-negligible role in the development of PCa (21,22). Prostate cancer antigen 3 (PCA3), as one of the LncRNAs, has been proven to be a diagnostic marker to improve the diagnostic efficacy of PSA in PCa and has been approved by the FDA to guide repeated prostate biopsy (23,24). The lncRNA sequence contains nucleic acid binding sites and can be folded to form higher-level structures with corresponding protein-binding sites, which interacts with DNA, RNA, and proteins to affect the regulation of body functions (15,16).…”

MicroRNAs as Epigenetic Determinants of Treatment Response and Potential Therapeutic Targets in Prostate Cancer

“…A major constraint is related to the need for safe and efficient delivery systems able to guarantee an enhanced cell type-specific delivery. Different miRNA delivery systems have been proposed thus far, and some of them have demonstrated the ability to inhibit tumor growth in in vivo models of PCa [ 65 , 165 , 166 , 167 , 168 ]. Additional challenges in developing miRNA-based therapeutics are related to the need for a more detailed understanding of the functions exerted by specific miRNAs and the precise identification of their key targets relevant to PCa.…”

“…Interestingly, miRNAs have been largely implicated in the regulation of several processes underlying the development of different types of cancer, including PCa [ 64 ]. Dozens of miRNAs have been reported as deregulated in PCa tissues and cells compared to normal prostate, and for many of them a functional role has been described [ 65 ].…”

Plasma-Derived Exosome MiR-19b Acts as a Diagnostic Marker for Pancreatic Cancer

“…Several blood-derived exosome markers have been developed and show potential diagnostic value in Pca ( 5 , 9 ). Circulating miRNAs serve as diagnostic biomarkers in multiple types of cancers, including biliary tract cancer ( 10 ), colorectal cancer (CRC) ( 11 ), Pca ( 5 , 12 ), glioblastoma ( 13 ), prostate cancer ( 14 ), lung cancer ( 15 ), hepatocellular carcinoma ( 16 ), and other tumors ( 17 ). Unlike the multiple reports on circulating miRNAs, only a few studies have reported the diagnostic values of plasma- or serum-derived exosome miRNAs in Pca ( 18 , 19 ).…”