Title:MicroRNA Regulation of Androgen Receptor in Castration-Resistant Prostate Cancer: Premises, Promises, and Potentials
Volume: 14
Author(s): Safieh Ebrahimi, Seyed Isaac Hashemy, Amirhossein Sahebkar and Seyed Hamid Aghaee Bakhtiari*
Affiliation:
- Bioinformatics Research Group, Mashhad University of Medical Sciences, Mashhad,,Iran
Keywords:
Prostate cancer, castration-resistance, androgen receptor, microRNA, androgen deprivation therapy, combination
therapy.
Abstract: Prostate cancer (PCa) is the second most prevalent cancer and the fifth leading cause of
cancer-related deaths among men. Androgen deprivation therapy (ADT) is the most frequently
used therapeutic strategy in PCa; however, the development of resistance to ADT, known as castration-
resistant prostate cancer (CRPC), continues to be a major obstacle against the successful treatment
of PCa. The abnormal activation of the androgen receptor (AR) signaling pathway has been
found as one of the main contributing factors to the development of resistance in CRPC. Therefore,
AR regulatory strategies are urgently required to combat resistance. Recently, microRNAs (miRNAs)
have been found as major AR regulatory factors affecting ADT resistance. MiRNAs can target
AR itself, AR-related genes, AR splice variants, AR-related signaling pathways as well as cancer
stem cells (CSCs), and play critical roles in regulating ADT resistance. Due to their capability
to affect various genes and signaling pathways, miRNAs are now being studied for their potential
role as a new therapeutic target in CRPC. It has been recommended that combination therapies, including
miRNAs and existing drugs, can synergistically decrease castration resistance. miRNAs also
have prognostic values for ADT, and their expression profiling in CRPC patients before therapeutic
scheduling may enable the physician to diagnose patients who are ADT-resistant. Overall,
extant evidence obviously supports the predictive and therapeutic potential of miRNAs in CRPC
patients. This review summarizes the available information about the microRNA-mediated AR controlling
mechanisms involved in ADT resistance.