MiRNA 34a: a therapeutic target for castration-resistant prostate cancer

ABSTRACT

Introduction: Development of a therapy for bone metastases is of paramount importance for castration-resistant prostate cancer (CRPC). The osteomimetic properties of CRPC confer a propensity to metastasize to osseous sites. Micro-ribonucleic acid (miRNA) is non-coding RNA that acts as a post-transcriptional regulator of multiple proteins and associated pathways. Therefore identification of miRNAs could reveal a valid third generation therapy for CRPC.

Areas covered: miR34a has been found to play an integral role in the progression of prostate cancer, particularly in the regulation of metastatic genes involved in migration, intravasation, extravasation, bone attachment and bone homeostasis. The correlation between miR34a down-regulation and metastatic progression has generated substantial interest in this field.

Expert opinion: Examination of the evidence reveals that miR34a is an ideal target for gene therapy for metastatic CRPC. We also conclude that future studies should focus on the effects of miR34a upregulation in CRPC with respect to migration, translocation to bone micro-environment and osteomimetic phenotype development. The success of miR34a as a therapeutic is reliant on the development of appropriate delivery systems and targeting to the bone micro-environment. In tandem with any therapeutic studies, biomarker serum levels should also be ascertained as an indicator of successful miR34a delivery.

KEYWORDS:

• Castration-resistant prostate cancer
• genetic medicine
• metastases
• miR34a
• miRNA

Article highlights

• Prostate cancer is the second most prevalent cancer in men.

• Bone metastases significantly reduce life expectancy, and treatment options are mainly palliative.

• The deregulation of miRNAs has been implicated in the development and progression of prostate cancer.

• miR34a is downregulated in castration-resistant prostate cancer.

• The upregulation of miR34a is therefore a viable therapeutic.

• miR34a is presently in clinical trials in a liposomal formulation to treat liver and hematological malignancies.

• The design of an appropriate delivery system could enable miR34a to be delivered as an alternative therapy to those with metastatic prostate cancer.

This box summarizes the key points contained in the article.

Declaration of interest

MJ Chalanqui was supported by a Medical Research Council Studentship (MR/L015269/1). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.