Regulation Of The Androgen Signaling Pathway In Prostate Cancer By MicroRNAs
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Prostate cancer is the most common cancer in men and is dependent upon signaling from male hormones (androgens) for continued growth. We recently identified some novel small RNAs (intracellular messengers), called microRNAs, that are likley to play important roles in maintaining the androgen signaling pathway in prostate cancer. This project will evaluate the functional role of these microRNAs in human prostate cancer, and may provide the foundation for new avenues for therapeutic intervention.
Scleroderma or systemic sclerosis is a debilitating disease that is characterised by fibrosis of multiple organs leading to organ failure and eventually death. There is currently no cure for the disease. We are beginning to find that a newly-discovered class of molecules, called microRNAs, regulate many disease states but its role in scleroderma has not been established. We aim in this study to identify disease-related changes in microRNAs which may subsequently be used as therapeutic targets.
MicroRNA Regulation Of Sex Determination And Gonad Development.
Funder
National Health and Medical Research Council
Funding Amount
$518,076.00
Summary
Sex determination, the decision to develop into either boy or girl, influences most aspects of our lives. Consequently, disorders of sexual development (~1% of births), resulting in genital abnormalities, infertility and often cancer, are extremely traumatic for the individual. The molecular basis of these disorders is not well understood. This project will identify new factors important for sex determination and therefore will improve diagnosis and clinical care for the patients.
Human brain, pancreatic and head and neck cancers all have a poor prognosis. A gene critically implicated in these cancers is the epidermal growth factor receptor (EGFR), a key target for new therapies. We have identified a microRNA as a key regulator of the EGFR pathway in these tumors. In this project, we will investigate the functional role of this microRNA in these tumors, and determine if it can work synergistically with other new therapies targeting the EGFR pathway to improve outcomes.
In the past few years, an expanding number of small RNAs (ribonucleic acids) have been discovered that play a critical part in regulating multiple steps involved in the development of human tumors. One of the genes critically implicated in the development several human cancers (including breast, lung, brain, prostate and colon) is the epidermal growth factor receptor (EGFR). As a consequence, the EGFR is a key target for new biological therapies designed to reduce signaling through the EGFR path ....In the past few years, an expanding number of small RNAs (ribonucleic acids) have been discovered that play a critical part in regulating multiple steps involved in the development of human tumors. One of the genes critically implicated in the development several human cancers (including breast, lung, brain, prostate and colon) is the epidermal growth factor receptor (EGFR). As a consequence, the EGFR is a key target for new biological therapies designed to reduce signaling through the EGFR pathway resulting in reduced growth. Using a computer-based algorithm, we have recently discovered that one of these small RNAs (or microRNAs) is a master regulator of EGFR levels in human breast and lung cancer. When we add the specific microRNA to cancer cells with excess EGFRs and low levels of microRNA, we can abolish EGFR expression almost completely, associated with cell death. From our studies, it appears that the level of this microRNA in tissues relates inversely to the level of EGFR. As the major site of expression of this microRNA is in the brain, we were intrigued to demonstrate that the normally high level of the microRNA is lost in brain cancers (or gliomas) which are associated with high levels of EGFR. Thus, the loss of microRNA may enable the tumor to develop, suggesting that the microRNA may act as a tumor-suppressor . In this project, we will investigate the functional role of this microRNA in a range of human tumors, determine if it can work synergistically with other new biological therapies targeting the EGFR signaling pathway, identify some of its binding partners and determine the levels of EGFR and the microRNA prospectively in a cohort of gliomas. These studies will determine the functional role of the microRNA and form the foundation for further studies to consider strategies to deliver the microRNA for therapeutics.Read moreRead less