Crosstalk between Long Non Coding RNAs, microRNAs and DNA Damage Repair in Prostate Cancer: New Therapeutic Opportunities?

SIMPLE SUMMARY: Non-coding RNAs are a type of genetic material that doesn’t make protein, but performs diverse regulatory functions. In prostate cancer, most treatments target proteins, and resistance to such therapies is common, leading to disease progression. Targeting non-coding RNAs may provide alterative treatment options and potentially overcome drug resistance. Major types of non-coding RNAs include tiny ‘microRNAs’ and much longer ‘long non-coding RNAs’. Scientific studies have shown that these form a major part of the human genome, and play key roles in altering gene activity and determining the fate of cells. Importantly, in cancer, their activity is altered. Recent evidence suggests that microRNAs and long non-coding RNAs play important roles in controlling response to DNA damage. In this review, we explore how different types of non-coding RNA interact to control cell DNA damage responses, and how this knowledge may be used to design better prostate cancer treatments and tests. 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.