Abstract
It is increasingly appreciated that transcripts derived from non-coding parts of the human genome, such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), are key regulators of biological processes both in normal physiology and disease. Their dysregulation during tumourigenesis has attracted significant interest in their exploitation as novel cancer therapeutics. Prostate cancer (PCa), as one of the most diagnosed malignancies and a leading cause of cancer-related death in men, continues to pose a major public health problem. In particular, survival of men with metastatic disease is very poor. Defects in DNA damage response (DDR) pathways culminate in genomic instability in PCa, which is associated with aggressive disease and poor patient outcome. Treatment options for metastatic PCa remain limited. Thus, researchers are increasingly targeting ncRNAs and DDR pathways to develop new biomarkers and therapeutics for PCa. Increasing evidence points to a widespread and biologically-relevant regulatory network of interactions between lncRNAs and miRNAs, with implications for major biological and pathological processes. This review summarises the current state of knowledge surrounding the roles of the lncRNA:miRNA interactions in PCa DDR, and their emerging potential as predictive and diagnostic biomarkers. We also discuss their therapeutic promise for the clinical management of PCa.
Highlights
LncRNA CASC2 and SPRY2 were found to be down regulated while miR-183-5p was significantly upregulated in Pca tissues compared with adjacent benign tissues, and the down- and up-regulation respectively correlated with higher PSA levels, Gleason score, presence of metastases and shorter overall survival [114,116,117,118,119,120]
Whilst the approval of the Pfizer-BioNTech and Moderna mRNAbased COVID-19 vaccines in 2020 in response to the COVID-19 pandemic [210] has renewed interest in RNA-based therapeutics, miRNA-based drugs are yet to deliver on their therapeutic promise, with only a handful progressing to Phase I or II clinical trials
It is increasingly well-appreciated that miRNA activity is regulated by interactions with long non-coding RNAs (lncRNAs) within complex regulatory networks to exert exquisite control of gene expression
Summary
Prostate cancer (PCa) is the most prevalent male cancer in the Western world and the second most frequent malignancy in men worldwide [1,2]. Androgen deprivation therapy (ADT), which blocks androgen synthesis and/or inhibits AR action, remains the mainstay treatment of localised or locally-advanced intermediate/high-risk and recurrent disease. Treatment options in all cases are limited, but second-generation anti-androgens/androgensynthesis inhibitors such as enzalutamide and abiraterone respectively, have been shown to increase survival [5,6,7]. Their efficacy has resulted in their approval for use at earlier disease stages: abiraterone plus prednisone in non-metastatic CRPC [8], and enzalutamide for low-volume disease or prior to docetaxel treatment in metastatic hormone-sensitive. There is a need to explore novel pathways in disease management
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
