Therapeutic microRNA control of Prostate Cancer growth

Key Information

Cancer type: 
Prostate
Research Institution: 
NUIG
Grant Amount: 
€125,070
Start date: 
July 1, 2011
End date: 
December 31, 2013

Scientific Project Abstract

Every year, prostate cancer kills more than 500 men in Ireland and over 250,000 men worldwide. It is the most commonly diagnosed cancer in Ireland accounting for 23% of all new cancers in men. Prostate cancer depends on androgens for growth therefore androgen deprivation by castration (chemical or surgical) represents the primary treatment for this disease. However, prostate cancer cells can gain the ability to grow in the absence of androgens, causing an irreversible conversion to castration-resistant prostate cancer (CRPC), which is fatal within 12-18months. While several promising drugs in clinical trials can extend the lifespan of CRPC by 4-6 months, no current therapies are aimed at preventing the emergence of fatal CRPC. To combat this disease it is critical to understand the molecular events that make individuals susceptible to or protect individuals from CRPC. We propose molecules called microRNAs (miRNAs) regulate prostate cancer progression to CRPC. miRNAs have been shown to be up regulated or down regulated in prostate tumours. Upregulated miRNAs could inhibit proteins important in protecting against cancer, whereas down regulated miRNAs may cause an increase in oncogenic (cancer causing) proteins both of these scenarios contributing to cancer progression. To support this theory we have found that miRNA-206 levels go down in prostate cancer and reintroduction of miRNA-206 into prostate cancer cells causes them to stop growing. Furthermore we show that miRNA-206 directly binds and inhibits a renowned oncogene, Cyclin D1. Thus we propose miRNA-206 functions as an important tumour suppressor in prostate cells by regulating Cyclin D1. The specific aim of this study will test our hypothesis by manipulating miRNA-206 in normal and prostate cancer cells to determine its potential in controlling Cyclin D1 and prostate cancer progression. These studies will help us understand how correct regulation of Cyclin D1 by miRNA-206 is required to control prostate cancer growth. Thus this work has the potential to identify new treatments for prostate cancer. Theoretically, miRNA therapies that inhibit Cyclin D1 or miRNAs inhibitors that prevent CRPC could be used in combination with androgen deprivation therapy to treat prostate cancer patients. The long-term goal of this proposal is to develop new and better interventions for prostate cancer prevention, early detection, and treatment.

For the non-scientist

One-line description: 
Investigating the role of small gene regulators in prostate cancer progression
What this project involves: 

Prostate cancer depends on androgens for growth therefore androgen deprivation by castration represents the primary treatment for this disease. However, prostate cancer cells can gain the ability to grow in the absence of androgens, causing an irreversible conversion to castration-resistant prostate cancer (CRPC) which is a fatal disease. This project aims to identify genetic regulators which control this conversion to CRPC.